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image of The Therapeutic Potential of Targeting Tumor Microenvironment and Modulation of Immunotherapy in Gastrointestinal Cancer

Abstract

Immunotherapy, as a novel treatment approach for various disorders, including cancers, is designed to either stimulate or suppress the immune system with high specificity. The recent achievements of this therapy in clinical trials are set to transform traditional treatment methods. Furthermore, it holds promise for enhancing the survival rates of patients suffering from both metastatic cancers and primary stages. Gastrointestinal Cancers (GI) account for 26% of global incidence and 35% of worldwide deaths. Treatment can be carried out using targeted immunotherapy in these cancers. If the tiers are superior, improvement could require more enterprise. On account that the function of immunotherapy in GI has been so promising, solely in sufferers with severe metastatic levels, within the literature, the immune checkpoint inhibitors in cancer immunotherapy of GI cancers, chimeric antigen receptor T-cell (vehicle-T), modulators of the tumor microenvironment, and drug resistance mechanisms in immunotherapy as an effective treatment approach to GI cancers along with colon, pancreas, gastric, and esophageal cancers have been addressed. This review provides an overview of FDA-approved immunotherapy drugs and ongoing preclinical developments. Additionally, we offer insights into the future of immunotherapy for GI cancer patients, addressing the associated challenges.

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2024-09-30
2025-04-06

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References

  1. van den Bulk J. Verdegaal E.M.E. de Miranda N.F.C.C. Cancer immunotherapy: Broadening the scope of targetable tumours. Open Biol. 2018 8 6 180037 10.1098/rsob.180037 29875199
    [Google Scholar]
  2. Köhler G. Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 1975 256 5517 495 497 10.1038/256495a0 1172191
    [Google Scholar]
  3. Burnet F.M. Immunological aspects of malignant disease. Lancet 1967 289 7501 1171 1174 10.1016/S0140‑6736(67)92837‑1 4165129
    [Google Scholar]
  4. Maloney D.G. Grillo-López A.J. White C.A. Bodkin D. Schilder R.J. Neidhart J.A. Janakiraman N. Foon K.A. Liles T.M. Dallaire B.K. Wey K. Royston I. Davis T. Levy R. IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin’s lymphoma. Blood 1997 90 6 2188 2195 10.1182/blood.V90.6.2188 9310469
    [Google Scholar]
  5. Kochenderfer J.N. Dudley M.E. Kassim S.H. Somerville R.P.T. Carpenter R.O. Stetler-Stevenson M. Yang J.C. Phan G.Q. Hughes M.S. Sherry R.M. Raffeld M. Feldman S. Lu L. Li Y.F. Ngo L.T. Goy A. Feldman T. Spaner D.E. Wang M.L. Chen C.C. Kranick S.M. Nath A. Nathan D.A.N. Morton K.E. Toomey M.A. Rosenberg S.A. Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor. J. Clin. Oncol. 2015 33 6 540 549 10.1200/JCO.2014.56.2025 25154820
    [Google Scholar]
  6. Kochenderfer J.N. Wilson W.H. Janik J.E. Dudley M.E. Stetler-Stevenson M. Feldman S.A. Maric I. Raffeld M. Nathan D.A.N. Lanier B.J. Morgan R.A. Rosenberg S.A. Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. Blood 2010 116 20 4099 4102 10.1182/blood‑2010‑04‑281931 20668228
    [Google Scholar]
  7. Khoshghamat N. Jafari N. Moetamani-Ahmadi M. Khalili-Tanha G. Khajavi rad M.H. Sahebdel S. Khalili-Tanha N. Soleimanpour S. Khazaei M. Hassanian S.M. Ferns G.A. Avan A. Programmed cell death 1 as prognostic marker and therapeutic target in upper gastrointestinal cancers. Pathol. Res. Pract. 2021 220 153390 10.1016/j.prp.2021.153390 33640713
    [Google Scholar]
  8. Sangani P.S. Yazdani S. Khalili-Tanha G. Ghorbani E. Al-Hayawi I.S. Fiuji H. Khazaei M. Hassanian S.M. Kiani M. Ghayour-Mobarhan M. Ferns G.A. Nazari E. Avan A. The therapeutic impact of programmed death – 1 in the treatment of colorectal cancer. Pathol. Res. Pract. 2024 259 155345 10.1016/j.prp.2024.155345 38805760
    [Google Scholar]
  9. Esfahani K. Roudaia L. Buhlaiga N. Del Rincon S.V. Papneja N. Miller W.H. Jr A review of cancer immunotherapy: From the past, to the present, to the future. Curr. Oncol. 2020 27 12 Suppl. 2 87 97 10.3747/co.27.5223 32368178
    [Google Scholar]
  10. Riley R.S. June C.H. Langer R. Mitchell M.J. Delivery technologies for cancer immunotherapy. Nat. Rev. Drug Discov. 2019 18 3 175 196 10.1038/s41573‑018‑0006‑z 30622344
    [Google Scholar]
  11. Ventola C.L. Cancer Immunotherapy, Part 1: Current Strategies and Agents. P&T 2017 42 6 375 383 28579724
    [Google Scholar]
  12. Tay R.E. Richardson E.K. Toh H.C. Revisiting the role of CD4+ T cells in cancer immunotherapy—new insights into old paradigms. Cancer Gene Ther. 2021 28 1-2 5 17 10.1038/s41417‑020‑0183‑x 32457487
    [Google Scholar]
  13. Kotsias F. Cebrian I. Alloatti A. Antigen processing and presentation. Int. Rev. Cell Mol. Biol. 2019 348 69 121 10.1016/bs.ircmb.2019.07.005 31810556
    [Google Scholar]
  14. Lee M.Y. Jeon J.W. Sievers C. Allen C.T. Antigen processing and presentation in cancer immunotherapy. J. Immunother. Cancer 2020 8 2 e001111 10.1136/jitc‑2020‑001111 32859742
    [Google Scholar]
  15. Sadeghi Rad H. Monkman J. Warkiani M.E. Ladwa R. O’Byrne K. Rezaei N. Kulasinghe A. Understanding the tumor microenvironment for effective immunotherapy. Med. Res. Rev. 2021 41 3 1474 1498 10.1002/med.21765 33277742
    [Google Scholar]
  16. Escors D. Tumour immunogenicity, antigen presentation, and immunological barriers in cancer immunotherapy. New J. Sci. 2014 2014 734515 10.1155/2014/734515
    [Google Scholar]
  17. Ashique S. Garg A. Mishra N. Raina N. Ming L.C. Tulli H.S. Behl T. Rani R. Gupta M. Nano-mediated strategy for targeting and treatment of non-small cell lung cancer (NSCLC). Naunyn Schmiedebergs Arch. Pharmacol. 2023 396 11 2769 2792 10.1007/s00210‑023‑02522‑5 37219615
    [Google Scholar]
  18. Sambi M. Bagheri L. Szewczuk M.R. Current Challenges in Cancer Immunotherapy: Multimodal Approaches to Improve Efficacy and Patient Response Rates. J. Oncol. 2019 2019 1 12 10.1155/2019/4508794 30941175
    [Google Scholar]
  19. Chandran S.S. Klebanoff C.A. T cell receptor‐based cancer immunotherapy: Emerging efficacy and pathways of resistance. Immunol. Rev. 2019 290 1 127 147 10.1111/imr.12772 31355495
    [Google Scholar]
  20. Cornel A.M. Mimpen I.L. Nierkens S. MHC Class I Downregulation in Cancer: Underlying Mechanisms and Potential Targets for Cancer Immunotherapy. Cancers (Basel) 2020 12 7 1760 10.3390/cancers12071760 32630675
    [Google Scholar]
  21. Berraondo P. Sanmamed M.F. Ochoa M.C. Etxeberria I. Aznar M.A. Pérez-Gracia J.L. Rodríguez-Ruiz M.E. Ponz-Sarvise M. Castañón E. Melero I. Cytokines in clinical cancer immunotherapy. Br. J. Cancer 2019 120 1 6 15 10.1038/s41416‑018‑0328‑y 30413827
    [Google Scholar]
  22. Christofi T. Baritaki S. Falzone L. Libra M. Zaravinos A. Current Perspectives in Cancer Immunotherapy. Cancers (Basel) 2019 11 10 1472 10.3390/cancers11101472 31575023
    [Google Scholar]
  23. Ventola C.L. Cancer Immunotherapy, Part 3: Challenges and Future Trends. P&T 2017 42 8 514 521 28781505
    [Google Scholar]
  24. Zhang H. Chen J. Current status and future directions of cancer immunotherapy. J. Cancer 2018 9 10 1773 1781 10.7150/jca.24577 29805703
    [Google Scholar]
  25. Liu J. Li H. Zhang N. Dong Q. Liang Z. Multiomics Analysis of Disulfidptosis Patterns and Integrated Machine Learning to Predict Immunotherapy Response in Lung Adenocarcinoma. Curr. Med. Chem. 2024 38685772
    [Google Scholar]
  26. Singh S.S. Dahal A. Shrestha L. Jois S.D. Genotype driven therapy for non-small cell lung cancer: Resistance, pan inhibitors and immunotherapy. Curr. Med. Chem. 2020 27 32 5274 5316 10.2174/0929867326666190222183219 30854949
    [Google Scholar]
  27. Tekguc M. Wing J.B. Osaki M. Long J. Sakaguchi S. Treg-expressed CTLA-4 depletes CD80/CD86 by trogocytosis, releasing free PD-L1 on antigen-presenting cells. Proc. Natl. Acad. Sci. USA 2021 118 30 e2023739118 10.1073/pnas.2023739118 34301886
    [Google Scholar]
  28. Adashek J.J. Kato S. Ferrara R. Lo Russo G. Kurzrock R. Hyperprogression and Immune Checkpoint Inhibitors: Hype or Progress? Oncologist 2020 25 2 94 98 10.1634/theoncologist.2019‑0636 32043794
    [Google Scholar]
  29. Díaz-Serrano A. Angulo B. Dominguez C. Pazo-Cid R. Salud A. Jiménez-Fonseca P. Leon A. Galan M.C. Alsina M. Rivera F. Plaza J.C. Paz-Ares L. Lopez-Rios F. Gómez-Martín C. Genomic Profiling of HER2-Positive Gastric Cancer: PI3K/Akt/mTOR Pathway as Predictor of Outcomes in HER2-Positive Advanced Gastric Cancer Treated with Trastuzumab. Oncologist 2018 23 9 1092 1102 10.1634/theoncologist.2017‑0379 29700210
    [Google Scholar]
  30. Keld R. Guo B. Downey P. Gulmann C. Ang Y.S. Sharrocks A.D. The ERK MAP kinase-PEA3/ETV4-MMP-1 axis is operative in oesophageal adenocarcinoma. Mol. Cancer 2010 9 1 313 10.1186/1476‑4598‑9‑313 21143918
    [Google Scholar]
  31. Shan J. Han D. Shen C. Lei Q. Zhang Y. Mechanism and strategies of immunotherapy resistance in colorectal cancer. Front. Immunol. 2022 13 1016646 10.3389/fimmu.2022.1016646 36238278
    [Google Scholar]
  32. Smith L.K. Boukhaled G.M. Condotta S.A. Mazouz S. Guthmiller J.J. Vijay R. Butler N.S. Bruneau J. Shoukry N.H. Krawczyk C.M. Richer M.J. Interleukin-10 Directly Inhibits CD8+ T Cell Function by Enhancing N-Glycan Branching to Decrease Antigen Sensitivity. Immunity 2018 48 2 299 312.e5 10.1016/j.immuni.2018.01.006 29396160
    [Google Scholar]
  33. Oiseth S.J. Aziz M.S. Cancer immunotherapy: A brief review of the history, possibilities, and challenges ahead. J. Cancer Metastasis Treat. 2017 3 10 250 261 10.20517/2394‑4722.2017.41
    [Google Scholar]
  34. Ribas A. Wolchok J.D. Cancer immunotherapy using checkpoint blockade. Science 2018 359 6382 1350 1355 10.1126/science.aar4060 29567705
    [Google Scholar]
  35. Kennedy L.B. Salama A.K.S. A review of cancer immunotherapy toxicity. CA Cancer J. Clin. 2020 70 2 86 104 10.3322/caac.21596 31944278
    [Google Scholar]
  36. Waldmann T.A. Cytokines in Cancer Immunotherapy. Cold Spring Harb. Perspect. Biol. 2018 10 12 a028472 10.1101/cshperspect.a028472 29101107
    [Google Scholar]
  37. Bear A.S. Vonderheide R.H. O’Hara M.H. Challenges and Opportunities for Pancreatic Cancer Immunotherapy. Cancer Cell 2020 38 6 788 802 10.1016/j.ccell.2020.08.004 32946773
    [Google Scholar]
  38. Thorsson V. Gibbs D.L. Brown S.D. Wolf D. Bortone D.S. Ou Yang T.H. Porta-Pardo E. Gao G.F. Plaisier C.L. Eddy J.A. Ziv E. Culhane A.C. Paull E.O. Sivakumar I.K.A. Gentles A.J. Malhotra R. Farshidfar F. Colaprico A. Parker J.S. Mose L.E. Vo N.S. Liu J. Liu Y. Rader J. Dhankani V. Reynolds S.M. Bowlby R. Califano A. Cherniack A.D. Anastassiou D. Bedognetti D. Mokrab Y. Newman A.M. Rao A. Chen K. Krasnitz A. Hu H. Malta T.M. Noushmehr H. Pedamallu C.S. Bullman S. Ojesina A.I. Lamb A. Zhou W. Shen H. Choueiri T.K. Weinstein J.N. Guinney J. Saltz J. Holt R.A. Rabkin C.S. Lazar A.J. Serody J.S. Demicco E.G. Disis M.L. Vincent B.G. Shmulevich I. Caesar-Johnson S.J. Demchok J.A. Felau I. Kasapi M. Ferguson M.L. Hutter C.M. Sofia H.J. Tarnuzzer R. Wang Z. Yang L. Zenklusen J.C. Zhang J.J. Chudamani S. Liu J. Lolla L. Naresh R. Pihl T. Sun Q. Wan Y. Wu Y. Cho J. DeFreitas T. Frazer S. Gehlenborg N. Getz G. Heiman D.I. Kim J. Lawrence M.S. Lin P. Meier S. Noble M.S. Saksena G. Voet D. Zhang H. Bernard B. Chambwe N. Dhankani V. Knijnenburg T. Kramer R. Leinonen K. Liu Y. Miller M. Reynolds S. Shmulevich I. Thorsson V. Zhang W. Akbani R. Broom B.M. Hegde A.M. Ju Z. Kanchi R.S. Korkut A. Li J. Liang H. Ling S. Liu W. Lu Y. Mills G.B. Ng K-S. Rao A. Ryan M. Wang J. Weinstein J.N. Zhang J. Abeshouse A. Armenia J. Chakravarty D. Chatila W.K. de Bruijn I. Gao J. Gross B.E. Heins Z.J. Kundra R. La K. Ladanyi M. Luna A. Nissan M.G. Ochoa A. Phillips S.M. Reznik E. Sanchez-Vega F. Sander C. Schultz N. Sheridan R. Sumer S.O. Sun Y. Taylor B.S. Wang J. Zhang H. Anur P. Peto M. Spellman P. Benz C. Stuart J.M. Wong C.K. Yau C. Hayes D.N. Parker J.S. Wilkerson M.D. Ally A. Balasundaram M. Bowlby R. Brooks D. Carlsen R. Chuah E. Dhalla N. Holt R. Jones S.J.M. Kasaian K. Lee D. Ma Y. Marra M.A. Mayo M. Moore R.A. Mungall A.J. Mungall K. Robertson A.G. Sadeghi S. Schein J.E. Sipahimalani P. Tam A. Thiessen N. Tse K. Wong T. Berger A.C. Beroukhim R. Cherniack A.D. Cibulskis C. Gabriel S.B. Gao G.F. Ha G. Meyerson M. Schumacher S.E. Shih J. Kucherlapati M.H. Kucherlapati R.S. Baylin S. Cope L. Danilova L. Bootwalla M.S. Lai P.H. Maglinte D.T. Van Den Berg D.J. Weisenberger D.J. Auman J.T. Balu S. Bodenheimer T. Fan C. Hoadley K.A. Hoyle A.P. Jefferys S.R. Jones C.D. Meng S. Mieczkowski P.A. Mose L.E. Perou A.H. Perou C.M. Roach J. Shi Y. Simons J.V. Skelly T. Soloway M.G. Tan D. Veluvolu U. Fan H. Hinoue T. Laird P.W. Shen H. Zhou W. Bellair M. Chang K. Covington K. Creighton C.J. Dinh H. Doddapaneni H.V. Donehower L.A. Drummond J. Gibbs R.A. Glenn R. Hale W. Han Y. Hu J. Korchina V. Lee S. Lewis L. Li W. Liu X. Morgan M. Morton D. Muzny D. Santibanez J. Sheth M. Shinbrot E. Wang L. Wang M. Wheeler D.A. Xi L. Zhao F. Hess J. Appelbaum E.L. Bailey M. Cordes M.G. Ding L. Fronick C.C. Fulton L.A. Fulton R.S. Kandoth C. Mardis E.R. McLellan M.D. Miller C.A. Schmidt H.K. Wilson R.K. Crain D. Curley E. Gardner J. Lau K. Mallery D. Morris S. Paulauskis J. Penny R. Shelton C. Shelton T. Sherman M. Thompson E. Yena P. Bowen J. Gastier-Foster J.M. Gerken M. Leraas K.M. Lichtenberg T.M. Ramirez N.C. Wise L. Zmuda E. Corcoran N. Costello T. Hovens C. Carvalho A.L. de Carvalho A.C. Fregnani J.H. Longatto-Filho A. Reis R.M. Scapulatempo-Neto C. Silveira H.C.S. Vidal D.O. Burnette A. Eschbacher J. Hermes B. Noss A. Singh R. Anderson M.L. Castro P.D. Ittmann M. Huntsman D. Kohl B. Le X. Thorp R. Andry C. Duffy E.R. Lyadov V. Paklina O. Setdikova G. Shabunin A. Tavobilov M. McPherson C. Warnick R. Berkowitz R. Cramer D. Feltmate C. Horowitz N. Kibel A. Muto M. Raut C.P. Malykh A. Barnholtz-Sloan J.S. Barrett W. Devine K. Fulop J. Ostrom Q.T. Shimmel K. Wolinsky Y. Sloan A.E. De Rose A. Giuliante F. Goodman M. Karlan B.Y. Hagedorn C.H. Eckman J. Harr J. Myers J. Tucker K. Zach L.A. Deyarmin B. Hu H. Kvecher L. Larson C. Mural R.J. Somiari S. Vicha A. Zelinka T. Bennett J. Iacocca M. Rabeno B. Swanson P. Latour M. Lacombe L. Têtu B. Bergeron A. McGraw M. Staugaitis S.M. Chabot J. Hibshoosh H. Sepulveda A. Su T. Wang T. Potapova O. Voronina O. Desjardins L. Mariani O. Roman-Roman S. Sastre X. Stern M-H. Cheng F. Signoretti S. Berchuck A. Bigner D. Lipp E. Marks J. McCall S. McLendon R. Secord A. Sharp A. Behera M. Brat D.J. Chen A. Delman K. Force S. Khuri F. Magliocca K. Maithel S. Olson J.J. Owonikoko T. Pickens A. Ramalingam S. Shin D.M. Sica G. Van Meir E.G. Zhang H. Eijckenboom W. Gillis A. Korpershoek E. Looijenga L. Oosterhuis W. Stoop H. van Kessel K.E. Zwarthoff E.C. Calatozzolo C. Cuppini L. Cuzzubbo S. DiMeco F. Finocchiaro G. Mattei L. Perin A. Pollo B. Chen C. Houck J. Lohavanichbutr P. Hartmann A. Stoehr C. Stoehr R. Taubert H. Wach S. Wullich B. Kycler W. Murawa D. Wiznerowicz M. Chung K. Edenfield W.J. Martin J. Baudin E. Bubley G. Bueno R. De Rienzo A. Richards W.G. Kalkanis S. Mikkelsen T. Noushmehr H. Scarpace L. Girard N. Aymerich M. Campo E. Giné E. Guillermo A.L. Van Bang N. Hanh P.T. Phu B.D. Tang Y. Colman H. Evason K. Dottino P.R. Martignetti J.A. Gabra H. Juhl H. Akeredolu T. Stepa S. Hoon D. Ahn K. Kang K.J. Beuschlein F. Breggia A. Birrer M. Bell D. Borad M. Bryce A.H. Castle E. Chandan V. Cheville J. Copland J.A. Farnell M. Flotte T. Giama N. Ho T. Kendrick M. Kocher J-P. Kopp K. Moser C. Nagorney D. O’Brien D. O’Neill B.P. Patel T. Petersen G. Que F. Rivera M. Roberts L. Smallridge R. Smyrk T. Stanton M. Thompson R.H. Torbenson M. Yang J.D. Zhang L. Brimo F. Ajani J.A. Gonzalez A.M.A. Behrens C. Bondaruk J. Broaddus R. Czerniak B. Esmaeli B. Fujimoto J. Gershenwald J. Guo C. Lazar A.J. Logothetis C. Meric-Bernstam F. Moran C. Ramondetta L. Rice D. Sood A. Tamboli P. Thompson T. Troncoso P. Tsao A. Wistuba I. Carter C. Haydu L. Hersey P. Jakrot V. Kakavand H. Kefford R. Lee K. Long G. Mann G. Quinn M. Saw R. Scolyer R. Shannon K. Spillane A. Stretch Synott M. Thompson J. Wilmott J. Al-Ahmadie H. Chan T.A. Ghossein R. Gopalan A. Levine D.A. Reuter V. Singer S. Singh B. Tien N.V. Broudy T. Mirsaidi C. Nair P. Drwiega P. Miller J. Smith J. Zaren H. Park J-W. Hung N.P. Kebebew E. Linehan W.M. Metwalli A.R. Pacak K. Pinto P.A. Schiffman M. Schmidt L.S. Vocke C.D. Wentzensen N. Worrell R. Yang H. Moncrieff M. Goparaju C. Melamed J. Pass H. Botnariuc N. Caraman I. Cernat M. Chemencedji I. Clipca A. Doruc S. Gorincioi G. Mura S. Pirtac M. Stancul I. Tcaciuc D. Albert M. Alexopoulou I. Arnaout A. Bartlett J. Engel J. Gilbert S. Parfitt J. Sekhon H. Thomas G. Rassl D.M. Rintoul R.C. Bifulco C. Tamakawa R. Urba W. Hayward N. Timmers H. Antenucci A. Facciolo F. Grazi G. Marino M. Merola R. de Krijger R. Gimenez-Roqueplo A-P. Piché A. Chevalier S. McKercher G. Birsoy K. Barnett G. Brewer C. Farver C. Naska T. Pennell N.A. Raymond D. Schilero C. Smolenski K. Williams F. Morrison C. Borgia J.A. Liptay M.J. Pool M. Seder C.W. Junker K. Omberg L. Dinkin M. Manikhas G. Alvaro D. Bragazzi M.C. Cardinale V. Carpino G. Gaudio E. Chesla D. Cottingham S. Dubina M. Moiseenko F. Dhanasekaran R. Becker K-F. Janssen K-P. Slotta-Huspenina J. Abdel-Rahman M.H. Aziz D. Bell S. Cebulla C.M. Davis A. Duell R. Elder J.B. Hilty J. Kumar B. Lang J. Lehman N.L. Mandt R. Nguyen P. Pilarski R. Rai K. Schoenfield L. Senecal K. Wakely P. Hansen P. Lechan R. Powers J. Tischler A. Grizzle W.E. Sexton K.C. Kastl A. Henderson J. Porten S. Waldmann J. Fassnacht M. Asa S.L. Schadendorf D. Couce M. Graefen M. Huland H. Sauter G. Schlomm T. Simon R. Tennstedt P. Olabode O. Nelson M. Bathe O. Carroll P.R. Chan J.M. Disaia P. Glenn P. Kelley R.K. Landen C.N. Phillips J. Prados M. Simko J. Smith-McCune K. VandenBerg S. Roggin K. Fehrenbach A. Kendler A. Sifri S. Steele R. Jimeno A. Carey F. Forgie I. Mannelli M. Carney M. Hernandez B. Campos B. Herold-Mende C. Jungk C. Unterberg A. von Deimling A. Bossler A. Galbraith J. Jacobus L. Knudson M. Knutson T. Ma D. Milhem M. Sigmund R. Godwin A.K. Madan R. Rosenthal H.G. Adebamowo C. Adebamowo S.N. Boussioutas A. Beer D. Giordano T. Mes-Masson A-M. Saad F. Bocklage T. Landrum L. Mannel R. Moore K. Moxley K. Postier R. Walker J. Zuna R. Feldman M. Valdivieso F. Dhir R. Luketich J. Pinero E.M.M. Quintero-Aguilo M. Carlotti C.G. Jr Dos Santos J.S. Kemp R. Sankarankuty A. Tirapelli D. Catto J. Agnew K. Swisher E. Creaney J. Robinson B. Shelley C.S. Godwin E.M. Kendall S. Shipman C. Bradford C. Carey T. Haddad A. Moyer J. Peterson L. Prince M. Rozek L. Wolf G. Bowman R. Fong K.M. Yang I. Korst R. Rathmell W.K. Fantacone-Campbell J.L. Hooke J.A. Kovatich A.J. Shriver C.D. DiPersio J. Drake B. Govindan R. Heath S. Ley T. Van Tine B. Westervelt P. Rubin M.A. Lee J.I. Aredes N.D. Mariamidze A. The Immune Landscape of Cancer. Immunity 2018 48 4 812 830.e14 10.1016/j.immuni.2018.03.023 29628290
    [Google Scholar]
  39. Takahashi H. Kawaguchi T. Yan L. Peng X. Qi Q. Morris L.G.T. Chan T.A. Tsung A. Otsuji E. Takabe K. Immune Cytolytic Activity for Comprehensive Understanding of Immune Landscape in Hepatocellular Carcinoma. Cancers (Basel) 2020 12 5 1221 10.3390/cancers12051221 32414098
    [Google Scholar]
  40. Picard E. Verschoor C.P. Ma G.W. Pawelec G. Relationships Between Immune Landscapes, Genetic Subtypes and Responses to Immunotherapy in Colorectal Cancer. Front. Immunol. 2020 11 369 10.3389/fimmu.2020.00369 32210966
    [Google Scholar]
  41. Le X. Negrao M.V. Reuben A. Federico L. Diao L. McGrail D. Nilsson M. Robichaux J. Munoz I.G. Patel S. Elamin Y. Fan Y.H. Lee W.C. Parra E. Solis Soto L.M. Chen R. Li J. Karpinets T. Khairullah R. Kadara H. Behrens C. Sepesi B. Wang R. Zhu M. Wang L. Vaporciyan A. Roth J. Swisher S. Haymaker C. Zhang J. Wang J. Wong K.K. Byers L.A. Bernatchez C. Zhang J. Wistuba I.I. Gibbons D.L. Akbay E.A. Heymach J.V. Characterization of the Immune Landscape of EGFR-Mutant NSCLC Identifies CD73/Adenosine Pathway as a Potential Therapeutic Target. J. Thorac. Oncol. 2021 16 4 583 600 10.1016/j.jtho.2020.12.010 33388477
    [Google Scholar]
  42. Giraud J. Chalopin D. Blanc J.F. Saleh M. Hepatocellular Carcinoma Immune Landscape and the Potential of Immunotherapies. Front. Immunol. 2021 12 655697 10.3389/fimmu.2021.655697 33815418
    [Google Scholar]
  43. Huang T.X. Fu L. The immune landscape of esophageal cancer. Cancer Commun. (Lond.) 2019 39 1 79 10.1186/s40880‑019‑0427‑z 31771653
    [Google Scholar]
  44. Al Zein M. Boukhdoud M. Shammaa H. Mouslem H. El Ayoubi L.M. Iratni R. Issa K. Khachab M. Assi H.I. Sahebkar A. Eid A.H. Immunotherapy and immunoevasion of colorectal cancer. Drug Discov. Today 2023 28 9 103669 10.1016/j.drudis.2023.103669 37328052
    [Google Scholar]
  45. Jeught K.V. Xu H.C. Li Y.J. Lu X.B. Ji G. Drug resistance and new therapies in colorectal cancer. World J. Gastroenterol. 2018 24 34 3834 3848 10.3748/wjg.v24.i34.3834 30228778
    [Google Scholar]
  46. Sato Y. Fu Y. Liu H. Lee M.Y. Shaw M.H. Tumor-immune profiling of CT-26 and Colon 26 syngeneic mouse models reveals mechanism of anti-PD-1 response. BMC Cancer 2021 21 1 1222 10.1186/s12885‑021‑08974‑3 34774008
    [Google Scholar]
  47. Sahin I. George A. Zhang S. Huntington K.E. Ordulu Z. Zhou L. El-Deiry W.S. Hyperprogression of a mismatch repair-deficient colon cancer in a humanized mouse model following administration of immune checkpoint inhibitor pembrolizumab. Oncotarget 2021 12 21 2131 2146 10.18632/oncotarget.28086 34676046
    [Google Scholar]
  48. Chae Y.J. Kim J. Heo H. Woo C.W. Kim S.T. Kim M.J. Choi J.R. Kim D.H. Woo D.C. Kim K.W. Choi Y. Magnetic resonance colonography enables the efficacy assessment of immune checkpoint inhibitors in an orthotopic colorectal cancer mouse model. Transl. Oncol. 2019 12 9 1264 1270 10.1016/j.tranon.2019.06.006 31302474
    [Google Scholar]
  49. Zhong W. Myers J.S. Wang F. Wang K. Lucas J. Rosfjord E. Lucas J. Hooper A.T. Yang S. Lemon L.A. Guffroy M. May C. Bienkowska J.R. Rejto P.A. Comparison of the molecular and cellular phenotypes of common mouse syngeneic models with human tumors. BMC Genomics 2020 21 1 2 10.1186/s12864‑019‑6344‑3 31898484
    [Google Scholar]
  50. Agrawal K. Hill R.C. Wilkinson B.L. Allison P.B. Thomas C.E. Quantification of the anti-murine PD-1 monoclonal antibody RMP1-14 in BALB/c mouse plasma by liquid chromatography-tandem mass spectrometry and application to a pharmacokinetic study. Anal. Bioanal. Chem. 2020 412 3 739 752 10.1007/s00216‑019‑02292‑1 31832706
    [Google Scholar]
  51. Miyashita H. Kato S. Hong D.S. KRAS G12C inhibitor combination therapies: Current evidence and challenge. Front. Oncol. 2024 14 1380584 10.3389/fonc.2024.1380584 38756650
    [Google Scholar]
  52. Park J.J. Omiya R. Matsumura Y. Sakoda Y. Kuramasu A. Augustine M.M. Yao S. Tsushima F. Narazaki H. Anand S. Liu Y. Strome S.E. Chen L. Tamada K. B7-H1/CD80 interaction is required for the induction and maintenance of peripheral T-cell tolerance. Blood 2010 116 8 1291 1298 10.1182/blood‑2010‑01‑265975 20472828
    [Google Scholar]
  53. Zhang X.F. Pan K. Weng D.S. Chen C.L. Wang Q.J. Zhao J.J. Pan Q.Z. Liu Q. Jiang S.S. Li Y.Q. Zhang H.X. Xia J.C. Cytotoxic T lymphocyte antigen-4 expression in esophageal carcinoma: Implications for prognosis. Oncotarget 2016 7 18 26670 26679 10.18632/oncotarget.8476 27050369
    [Google Scholar]
  54. Hopkins A.C. Yarchoan M. Durham J.N. Yusko E.C. Rytlewski J.A. Robins H.S. Laheru D.A. Le D.T. Lutz E.R. Jaffee E.M. T cell receptor repertoire features associated with survival in immunotherapy-treated pancreatic ductal adenocarcinoma. JCI Insight 2018 3 13 e122092 10.1172/jci.insight.122092 29997287
    [Google Scholar]
  55. Sierro S. Romero P. Speiser D.E. The CD4-like molecule LAG-3, biology and therapeutic applications. Expert Opin. Ther. Targets 2011 15 1 91 101 10.1517/14712598.2011.540563 21142803
    [Google Scholar]
  56. Wang-Gillam A. Plambeck-Suess S. Goedegebuure P. Simon P.O. Mitchem J.B. Hornick J.R. Sorscher S. Picus J. Suresh R. Lockhart A.C. Tan B. Hawkins W.G. A phase I study of IMP321 and gemcitabine as the front-line therapy in patients with advanced pancreatic adenocarcinoma. Invest. New Drugs 2013 31 3 707 713 10.1007/s10637‑012‑9866‑y 22864469
    [Google Scholar]
  57. Chuong M. Chang E.T. Choi E.Y. Mahmood J. Lapidus R.G. Davila E. Carrier F. Exploring the concept of radiation “booster shot” in combination with an anti-PD-L1 mAb to enhance anti-tumor immune effects in mouse pancreas tumors. J. Clin. Oncol. Res. 2017 5 2 1058 30417086
    [Google Scholar]
  58. Yeong J. Lum H.Y.J. Teo C.B. Tan B.K.J. Chan Y.H. Tay R.Y.K. Choo J.R.E. Jeyasekharan A.D. Miow Q.H. Loo L.H. Yong W.P. Sundar R. Choice of PD-L1 immunohistochemistry assay influences clinical eligibility for gastric cancer immunotherapy. Gastric Cancer 2022 25 4 741 750 10.1007/s10120‑022‑01301‑0 35661944
    [Google Scholar]
  59. Fuchs C.S. Özgüroğlu M. Bang Y.J. Di Bartolomeo M. Mandala M. Ryu M.H. Fornaro L. Olesinski T. Caglevic C. Chung H.C. Muro K. Van Cutsem E. Elme A. Thuss-Patience P. Chau I. Ohtsu A. Bhagia P. Wang A. Shih C.S. Shitara K. Pembrolizumab versus paclitaxel for previously treated PD-L1-positive advanced gastric or gastroesophageal junction cancer: 2-year update of the randomized phase 3 KEYNOTE-061 trial. Gastric Cancer 2022 25 1 197 206 10.1007/s10120‑021‑01227‑z 34468869
    [Google Scholar]
  60. Kang B.W. Chau I. Current status and future potential of predictive biomarkers for immune checkpoint inhibitors in gastric cancer. ESMO Open 2020 5 4 e000791 10.1136/esmoopen‑2020‑000791 32817133
    [Google Scholar]
  61. Lee D. Choi J. Oh H.J. Ham I.H. Lee S.H. Nomura S. Han S.U. Hur H. Molecular and immune profiling of syngeneic mouse models predict response to immune checkpoint inhibitors in gastric cancer. Cancer Res. Treat. 2023 55 1 167 178 10.4143/crt.2022.094 35609622
    [Google Scholar]
  62. Liu X. Li X. Zhu C. Ji L. Effective control of postoperative recurrence of pregnancy-related gastric cancer using anti-PD-1 as a monotherapy: A case report. Front. Oncol. 2024 14 1321149 10.3389/fonc.2024.1321149 38800370
    [Google Scholar]
  63. Kashiwada T. Takano R. Ando F. Kuroda S. Miyabe Y. Owada R. Miyanaga A. Asatsuma-Okumura T. Hashiguchi M. Kanazawa Y. Yoshida H. Seike M. Gemma A. Iwai Y. Lysosomal degradation of PD-L1 is associated with immune-related adverse events during anti-PD-L1 immunotherapy in NSCLC patients. Front. Pharmacol. 2024 15 1384733 10.3389/fphar.2024.1384733 38799168
    [Google Scholar]
  64. Zhao Y. Wang J. Liu W.N. Fong S.Y. Shuen T.W.H. Liu M. Harden S. Tan S.Y. Cheng J.Y. Tan W.W.S. Chan J.K.Y. Chee C.E. Lee G.H. Toh H.C. Lim S.G. Wan Y. Chen Q. Analysis and validation of human targets and treatments using a hepatocellular carcinoma–immune humanized mouse model. Hepatology 2021 74 3 1395 1410 10.1002/hep.31812 33738839
    [Google Scholar]
  65. Zabransky D.J. Danilova L. Leatherman J.M. Lopez-Vidal T.Y. Sanchez J. Charmsaz S. Gross N.E. Shin S. Yuan X. Hernandez A. Yang H. Xavier S. Shu D. Saeed A. Munjal K. Kamdar Z. Kagohara L.T. Jaffee E.M. Yarchoan M. Ho W.J. Profiling of syngeneic mouse HCC tumor models as a framework to understand anti–PD‐1 sensitive tumor microenvironments. Hepatology 2023 77 5 1566 1579 10.1002/hep.32707 35941803
    [Google Scholar]
  66. Yuen V.W.H. Chiu D.K.C. Law C.T. Cheu J.W.S. Chan C.Y.K. Wong B.P.Y. Goh C.C. Zhang M.S. Xue H.D.G. Tse A.P.W. Zhang Y. Lau H.Y.H. Lee D. Au-Yeung R.K.H. Wong C.M. Wong C.C.L. Using mouse liver cancer models based on somatic genome editing to predict immune checkpoint inhibitor responses. J. Hepatol. 2023 78 2 376 389 10.1016/j.jhep.2022.10.037 36455783
    [Google Scholar]
  67. Yarchoan M. Cope L. Ruggieri A.N. Anders R.A. Noonan A.M. Goff L.W. Goyal L. Lacy J. Li D. Patel A.K. He A.R. Abou-Alfa G.K. Spencer K. Kim E.J. Davis S.L. McRee A.J. Kunk P.R. Goyal S. Liu Y. Dennison L. Xavier S. Mohan A.A. Zhu Q. Wang-Gillam A. Poklepovic A. Chen H.X. Sharon E. Lesinski G.B. Azad N.S. Multicenter randomized phase II trial of atezolizumab with or without cobimetinib in biliary tract cancers. J. Clin. Invest. 2021 131 24 e152670 10.1172/JCI152670 34907910
    [Google Scholar]
  68. Zheng Y. Mislang A.R.A. Coward J. Cosman R. Cooper A. Underhill C. Zhu J. Xiong J. Jiang O. Wang H. Xie Y. Zhou Y. Jin X. Li B. Wang Z.M. Kwek K.Y. Xia D. Xia Y. Xu N. Penpulimab, an anti-PD1 IgG1 antibody in the treatment of advanced or metastatic upper gastrointestinal cancers. Cancer Immunol. Immunother. 2022 71 10 2371 2379 10.1007/s00262‑022‑03160‑1 35165764
    [Google Scholar]
  69. Pedersen K.S. Foster N.R. Overman M.J. Boland P.M. Kim S.S. Arrambide K.A. Jaszewski B.L. Bekaii-Saab T. Graham R.P. Welch J. Wilson R.H. McWilliams R.R. ZEBRA: A Multicenter Phase II Study of Pembrolizumab in Patients with Advanced Small-Bowel Adenocarcinoma. Clin. Cancer Res. 2021 27 13 3641 3648 10.1158/1078‑0432.CCR‑21‑0159 33883178
    [Google Scholar]
  70. Chiang N.J. Tan K.T. Bai L.Y. Hsiao C.F. Huang C.Y. Hung Y.P. Huang C.J. Chen S.C. Shan Y.S. Chao Y. Huang Y.H. Lee I.C. Lee P.C. Su Y.Y. Chen S.J. Yeh C.N. Chen L.T. Chen M.H. Impaired chromatin remodeling predicts better survival to modified gemcitabine and S-1 plus nivolumab in advanced biliary tract cancer: A phase II T1219 study. Clin. Cancer Res. 2022 28 19 4248 4257 10.1158/1078‑0432.CCR‑22‑1152 35849151
    [Google Scholar]
  71. Khalili-Tanha G. Fiuji H. Gharib M. Moghbeli M. Khalili-Tanha N. Rahmani F. Shakour N. Maftooh M. Hassanian S.M. Asgharzadeh F. Shahidsales S. Anvari K. Mozafari M.R. Ferns G.A. Batra J. Giovannetti E. Khazaei M. Avan A. Dual targeting of TGF-β and PD-L1 inhibits tumor growth in TGF-β/PD-L1-driven colorectal carcinoma. Life Sci. 2023 328 121865 10.1016/j.lfs.2023.121865 37336360
    [Google Scholar]
  72. Land C.A. Musich P.R. Haydar D. Krenciute G. Xie Q. Chimeric antigen receptor T-cell therapy in glioblastoma: Charging the T cells to fight. J. Transl. Med. 2020 18 1 428 10.1186/s12967‑020‑02598‑0 33176788
    [Google Scholar]
  73. Mullaney B.P. Pallavicini M.G. Protein-protein interactions in hematology and phage display. Exp. Hematol. 2001 29 10 1136 1146 10.1016/S0301‑472X(01)00693‑2 11602315
    [Google Scholar]
  74. Abate-Daga D. Davila M.L. CAR models: Next-generation CAR modifications for enhanced T-cell function. Mol. Ther. Oncolytics 2016 3 16014 10.1038/mto.2016.14 27231717
    [Google Scholar]
  75. Maus M.V. Levine B.L. Chimeric Antigen Receptor T-Cell Therapy for the Community Oncologist. Oncologist 2016 21 5 608 617 10.1634/theoncologist.2015‑0421 27009942
    [Google Scholar]
  76. Greco B. Malacarne V. De Girardi F. Scotti G.M. Manfredi F. Angelino E. Sirini C. Camisa B. Falcone L. Moresco M.A. Paolella K. Di Bono M. Norata R. Sanvito F. Arcangeli S. Doglioni C. Ciceri F. Bonini C. Graziani A. Bondanza A. Casucci M. Disrupting N-glycan expression on tumor cells boosts chimeric antigen receptor T cell efficacy against solid malignancies. Sci. Transl. Med. 2022 14 628 eabg3072 10.1126/scitranslmed.abg3072 35044789
    [Google Scholar]
  77. Mukherji R. Yin C. Hameed R. Alqahtani A.Z. Kulasekaran M. He A.R. Weinberg B.A. Marshall J.L. Hartley M.L. Noel M.S. The current state of molecular profiling in gastrointestinal malignancies. Biol. Direct 2022 17 1 15 10.1186/s13062‑022‑00322‑0 35668531
    [Google Scholar]
  78. Yu F. Wang X. Shi H. Jiang M. Xu J. Sun M. Xu Q. Addai F.P. Shi H. Gu J. Zhou Y. Liu L. Development of chimeric antigen receptor-modified T cells for the treatment of esophageal cancer. Tumori 2021 107 4 341 352 10.1177/0300891620960223 32988314
    [Google Scholar]
  79. Picarda E. Ohaegbulam K.C. Zang X. Molecular pathways: Targeting B7-H3 (CD276) for human cancer immunotherapy. Clin. Cancer Res. 2016 22 14 3425 3431 10.1158/1078‑0432.CCR‑15‑2428 27208063
    [Google Scholar]
  80. Xuan Y. Sheng Y. Zhang D. Zhang K. Zhang Z. Ping Y. Wang S. Shi X. Lian J. Liu K. Zhang Y. Li F. Targeting CD276 by CAR-T cells induces regression of esophagus squamous cell carcinoma in xenograft mouse models. Transl. Oncol. 2021 14 8 101138 10.1016/j.tranon.2021.101138 34052626
    [Google Scholar]
  81. Shi H. Yu F. Mao Y. Ju Q. Wu Y. Bai W. Wang P. Xu R. Jiang M. Shi J. EphA2 chimeric antigen receptor-modified T cells for the immunotherapy of esophageal squamous cell carcinoma. J. Thorac. Dis. 2018 10 5 2779 2788 10.21037/jtd.2018.04.91 29997940
    [Google Scholar]
  82. Han Y. Liu C. Li G. Li J. Lv X. Shi H. Liu J. Liu S. Yan P. Wang S. Sun Y. Sun M. Antitumor effects and persistence of a novel HER2 CAR T cells directed to gastric cancer in preclinical models. Am. J. Cancer Res. 2018 8 1 106 119 29416924
    [Google Scholar]
  83. Zhang B.L. Li D. Gong Y.L. Huang Y. Qin D.Y. Jiang L. Liang X. Yang X. Gou H.F. Wang Y.S. Wei Y.Q. Wang W. Preclinical evaluation of chimeric antigen receptor–modified T cells specific to epithelial cell adhesion molecule for treating colorectal cancer. Hum. Gene Ther. 2019 30 4 402 412 10.1089/hum.2018.229 30693795
    [Google Scholar]
  84. Guo J. Tang Q. Recent updates on chimeric antigen receptor T cell therapy for hepatocellular carcinoma. Cancer Gene Ther. 2021 28 10-11 1075 1087 10.1038/s41417‑020‑00259‑4 33500535
    [Google Scholar]
  85. Jiang H. Shi Z. Wang P. Wang C. Yang L. Du G. Zhang H. Shi B. Jia J. Li Q. Wang H. Li Z. Claudin18.2-Specific Chimeric Antigen Receptor Engineered T Cells for the Treatment of Gastric Cancer. J. Natl. Cancer Inst. 2019 111 4 409 418 10.1093/jnci/djy134 30203099
    [Google Scholar]
  86. Zhan X. Wang B. Li Z. Li J. Wang H. Chen L. Phase I trial of Claudin 18.2-specific chimeric antigen receptor T cells for advanced gastric and pancreatic adenocarcinoma. J Clin Oncol 2019 37 15_suppl 2509
    [Google Scholar]
  87. Feng K. Liu Y. Guo Y. Qiu J. Wu Z. Dai H. Yang Q. Wang Y. Han W. Phase I study of chimeric antigen receptor modified T cells in treating HER2-positive advanced biliary tract cancers and pancreatic cancers. Protein Cell 2018 9 10 838 847 10.1007/s13238‑017‑0440‑4 28710747
    [Google Scholar]
  88. Du H Hirabayashi K Ahn S Kren NP Montgomery SA Wang X Antitumor responses in the absence of toxicity in solid tumors by targeting B7-H3 via chimeric antigen receptor T cells. Cancer Cell 2019 35 2 221 237.e8 10.1016/j.ccell.2019.01.002
    [Google Scholar]
  89. Beatty G.L. O’Hara M.H. Lacey S.F. Torigian D.A. Nazimuddin F. Chen F. Kulikovskaya I.M. Soulen M.C. McGarvey M. Nelson A.M. Gladney W.L. Levine B.L. Melenhorst J.J. Plesa G. June C.H. Activity of mesothelin-specific chimeric antigen receptor T cells against pancreatic carcinoma metastases in a phase 1 trial. Gastroenterology 2018 155 1 29 32 10.1053/j.gastro.2018.03.029 29567081
    [Google Scholar]
  90. Yang C.Y. Fan M.H. Miao C.H. Liao Y.J. Yuan R.H. Liu C.L. Engineering chimeric antigen receptor T cells against immune checkpoint inhibitors PD-1/PD-L1 for treating pancreatic cancer. Mol. Ther. Oncolytics 2020 17 571 585 10.1016/j.omto.2020.05.009 32637575
    [Google Scholar]
  91. Su Y.T. Chen J.W. Chang S.C. Jiang J.K. Huang S.C. The clinical experience of the prognosis in opposite CEA and image change after therapy in stage IV colorectal cancer. Sci. Rep. 2022 12 1 20075 10.1038/s41598‑022‑24187‑5 36418865
    [Google Scholar]
  92. Hege K.M. Bergsland E.K. Fisher G.A. Nemunaitis J.J. Warren R.S. McArthur J.G. Lin A.A. Schlom J. June C.H. Sherwin S.A. Safety, tumor trafficking and immunogenicity of chimeric antigen receptor (CAR)-T cells specific for TAG-72 in colorectal cancer. J. Immunother. Cancer 2017 5 1 22 10.1186/s40425‑017‑0222‑9 28344808
    [Google Scholar]
  93. Deng X. Gao F. Li N. Li Q. Zhou Y. Yang T. Cai Z. Du P. Chen F. Cai J. Antitumor activity of NKG2D CAR-T cells against human colorectal cancer cells in vitro and in vivo. Am. J. Cancer Res. 2019 9 5 945 958 31218103
    [Google Scholar]
  94. Akin Telli T. Bregni G. Camera S. Deleporte A. Hendlisz A. Sclafani F. PD-1 and PD-L1 inhibitors in oesophago-gastric cancers. Cancer Lett. 2020 469 142 150 10.1016/j.canlet.2019.10.036 31669518
    [Google Scholar]
  95. Hryniewicki A.T. Wang C. Shatsky R.A. Coyne C.J. Management of immune checkpoint inhibitor toxicities: A review and clinical guideline for emergency physicians. J. Emerg. Med. 2018 55 4 489 502 10.1016/j.jemermed.2018.07.005 30120013
    [Google Scholar]
  96. Lim S.Y. Rizos H. Immune cell profiling in the age of immune checkpoint inhibitors: Implications for biomarker discovery and understanding of resistance mechanisms. Mamm. Genome 2018 29 11-12 866 878 10.1007/s00335‑018‑9757‑4 29968076
    [Google Scholar]
  97. Sharma P. Hu-Lieskovan S. Wargo J.A. Ribas A. Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell 2017 168 4 707 723 10.1016/j.cell.2017.01.017 28187290
    [Google Scholar]
  98. Nowicki T.S. Hu-Lieskovan S. Ribas A. Mechanisms of resistance to PD-1 and PD-L1 blockade. Cancer J. 2018 24 1 47 53 10.1097/PPO.0000000000000303 29360728
    [Google Scholar]
  99. Sharma P. Allison J.P. The future of immune checkpoint therapy. Science 2015 348 6230 56 61 10.1126/science.aaa8172 25838373
    [Google Scholar]
  100. Kato K. Cho B.C. Takahashi M. Okada M. Lin C.Y. Chin K. Kadowaki S. Ahn M.J. Hamamoto Y. Doki Y. Yen C.C. Kubota Y. Kim S.B. Hsu C.H. Holtved E. Xynos I. Kodani M. Kitagawa Y. Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy (ATTRACTION-3): A multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019 20 11 1506 1517 10.1016/S1470‑2045(19)30626‑6 31582355
    [Google Scholar]
  101. Wang Z. Wu X. Study and analysis of antitumor resistance mechanism of PD1/PD‐L1 immune checkpoint blocker. Cancer Med. 2020 9 21 8086 8121 10.1002/cam4.3410 32875727
    [Google Scholar]
  102. Baba T. Hanagiri T. Ichiki Y. Kuroda K. Shigematsu Y. Mizukami M. Sugaya M. Takenoyama M. Sugio K. Yasumoto K. Lack and restoration of sensitivity of lung cancer cells to cellular attack with special reference to expression of human leukocyte antigen class I and/or major histocompatibility complex class I chain related molecules A/B. Cancer Sci. 2007 98 11 1795 1802 10.1111/j.1349‑7006.2007.00586.x 17725806
    [Google Scholar]
  103. Garrido F. Ruiz-Cabello F. Aptsiauri N. Rejection versus escape: The tumor MHC dilemma. Cancer Immunol. Immunother. 2017 66 2 259 271 10.1007/s00262‑016‑1947‑x 28040849
    [Google Scholar]
  104. Ito S. Okano S. Morita M. Saeki H. Tsutsumi S. Tsukihara H. Nakashima Y. Ando K. Imamura Y. Ohgaki K. Oki E. Kitao H. Mimori K. Maehara Y. Expression of PD-L1 and HLA class I in esophageal squamous cell carcinoma: Prognostic factors for patient outcome. Ann. Surg. Oncol. 2016 23 S4 Suppl. 4 508 515 10.1245/s10434‑016‑5376‑z 27380638
    [Google Scholar]
  105. García-Aranda M. Redondo M. Protein kinase targets in breast cancer. Int. J. Mol. Sci. 2017 18 12 2543 10.3390/ijms18122543 29186886
    [Google Scholar]
  106. García-Aranda M. Pérez-Ruiz E. Redondo M. Bcl-2 inhibition to overcome resistance to chemo-and immunotherapy. Int. J. Mol. Sci. 2018 19 12 3950 10.3390/ijms19123950 30544835
    [Google Scholar]
  107. García-Aranda M. Redondo M. Targeting protein kinases to enhance the response to anti-PD-1/PD-L1 immunotherapy. Int. J. Mol. Sci. 2019 20 9 2296 10.3390/ijms20092296 31075880
    [Google Scholar]
  108. Mansoori B. Mohammadi A. Davudian S. Shirjang S. Baradaran B. The different mechanisms of cancer drug resistance: A brief review. Adv. Pharm. Bull. 2017 7 3 339 348 10.15171/apb.2017.041 29071215
    [Google Scholar]
  109. Sade-Feldman M. Jiao Y.J. Chen J.H. Rooney M.S. Barzily-Rokni M. Eliane J.P. Bjorgaard S.L. Hammond M.R. Vitzthum H. Blackmon S.M. Frederick D.T. Hazar-Rethinam M. Nadres B.A. Van Seventer E.E. Shukla S.A. Yizhak K. Ray J.P. Rosebrock D. Livitz D. Adalsteinsson V. Getz G. Duncan L.M. Li B. Corcoran R.B. Lawrence D.P. Stemmer-Rachamimov A. Boland G.M. Landau D.A. Flaherty K.T. Sullivan R.J. Hacohen N. Resistance to checkpoint blockade therapy through inactivation of antigen presentation. Nat. Commun. 2017 8 1 1136 10.1038/s41467‑017‑01062‑w 29070816
    [Google Scholar]
  110. Sucker A. Zhao F. Pieper N. Heeke C. Maltaner R. Stadtler N. Real B. Bielefeld N. Howe S. Weide B. Gutzmer R. Utikal J. Loquai C. Gogas H. Klein-Hitpass L. Zeschnigk M. Westendorf A.M. Trilling M. Horn S. Schilling B. Schadendorf D. Griewank K.G. Paschen A. Acquired IFNγ resistance impairs anti-tumor immunity and gives rise to T-cell-resistant melanoma lesions. Nat. Commun. 2017 8 1 15440 10.1038/ncomms15440 28561041
    [Google Scholar]
  111. Spranger S. Bao R. Gajewski T.F. Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity. Nature 2015 523 7559 231 235 10.1038/nature14404 25970248
    [Google Scholar]
  112. Mouw K.W. Goldberg M.S. Konstantinopoulos P.A. D’Andrea A.D. DNA damage and repair biomarkers of immunotherapy response. Cancer Discov. 2017 7 7 675 693 10.1158/2159‑8290.CD‑17‑0226 28630051
    [Google Scholar]
  113. Rizvi N.A. Hellmann M.D. Snyder A. Kvistborg P. Makarov V. Havel J.J. Lee W. Yuan J. Wong P. Ho T.S. Miller M.L. Rekhtman N. Moreira A.L. Ibrahim F. Bruggeman C. Gasmi B. Zappasodi R. Maeda Y. Sander C. Garon E.B. Merghoub T. Wolchok J.D. Schumacher T.N. Chan T.A. Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer. Science 2015 348 6230 124 128 10.1126/science.aaa1348 25765070
    [Google Scholar]
  114. Curdy N. Lanvin O. Laurent C. Fournié J.J. Franchini D.M. Regulatory mechanisms of inhibitory immune checkpoint receptors expression. Trends Cell Biol. 2019 29 10 777 790 10.1016/j.tcb.2019.07.002 31378317
    [Google Scholar]
  115. Togashi Y. Nishikawa H. Regulatory T cells: Molecular and cellular basis for immunoregulation. Curr Top Microbiol Immunol. 2017 410 3 27
    [Google Scholar]
  116. Pan P.Y. Ma G. Weber K.J. Ozao-Choy J. Wang G. Yin B. Divino C.M. Chen S.H. Immune stimulatory receptor CD40 is required for T-cell suppression and T regulatory cell activation mediated by myeloid-derived suppressor cells in cancer. Cancer Res. 2010 70 1 99 108 10.1158/0008‑5472.CAN‑09‑1882 19996287
    [Google Scholar]
  117. Weber R. Fleming V. Hu X. Nagibin V. Groth C. Altevogt P. Utikal J. Umansky V. Myeloid-derived suppressor cells hinder the anti-cancer activity of immune checkpoint inhibitors. Front. Immunol. 2018 9 1310 10.3389/fimmu.2018.01310 29942309
    [Google Scholar]
  118. Cassetta L. Kitamura T. Targeting tumor-associated macrophages as a potential strategy to enhance the response to immune checkpoint inhibitors. Front. Cell Dev. Biol. 2018 6 38 10.3389/fcell.2018.00038 29670880
    [Google Scholar]
  119. Chen D.S. Mellman I. Elements of cancer immunity and the cancer–immune set point. Nature 2017 541 7637 321 330 10.1038/nature21349 28102259
    [Google Scholar]
  120. Mao C. Zeng X. Zhang C. Yang Y. Xiao X. Luan S. Zhang Y. Yuan Y. Mechanisms of pharmaceutical therapy and drug resistance in esophageal cancer. Front. Cell Dev. Biol. 2021 9 612451 10.3389/fcell.2021.612451 33644048
    [Google Scholar]
  121. Weiss G.J. Waypa J. Blaydorn L. Coats J. McGahey K. Sangal A. Niu J. Lynch C.A. Farley J.H. Khemka V. A phase Ib study of pembrolizumab plus chemotherapy in patients with advanced cancer (PembroPlus). Br. J. Cancer 2017 117 1 33 40 10.1038/bjc.2017.145 28588322
    [Google Scholar]
  122. Chowdhury P.S. Chamoto K. Honjo T. Combination therapy strategies for improving PD‐1 blockade efficacy: A new era in cancer immunotherapy. J. Intern. Med. 2018 283 2 110 120 10.1111/joim.12708 29071761
    [Google Scholar]
  123. Foley K. Kim V. Jaffee E. Zheng L. Current progress in immunotherapy for pancreatic cancer. Cancer Lett. 2016 381 1 244 251 10.1016/j.canlet.2015.12.020 26723878
    [Google Scholar]
  124. Vonderheide R.H. The immune revolution: A case for priming, not checkpoint. Cancer Cell 2018 33 4 563 569 10.1016/j.ccell.2018.03.008 29634944
    [Google Scholar]
  125. Dougan M. Ingram J.R. Jeong H.J. Mosaheb M.M. Bruck P.T. Ali L. Pishesha N. Blomberg O. Tyler P.M. Servos M.M. Rashidian M. Nguyen Q.D. von Andrian U.H. Ploegh H.L. Dougan S.K. Targeting cytokine therapy to the pancreatic tumor microenvironment using PD-L1–specific VHHs. Cancer Immunol. Res. 2018 6 4 389 401 10.1158/2326‑6066.CIR‑17‑0495 29459478
    [Google Scholar]
  126. Jiang H. Hegde S. Knolhoff B.L. Zhu Y. Herndon J.M. Meyer M.A. Nywening T.M. Hawkins W.G. Shapiro I.M. Weaver D.T. Pachter J.A. Wang-Gillam A. DeNardo D.G. Targeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy. Nat. Med. 2016 22 8 851 860 10.1038/nm.4123 27376576
    [Google Scholar]
  127. Kobold S. Grassmann S. Chaloupka M. Lampert C. Wenk S. Kraus F. Rapp M. Düwell P. Zeng Y. Schmollinger J.C. Schnurr M. Endres S. Rothenfußer S. Impact of a new fusion receptor on PD-1–mediated immunosuppression in adoptive T cell therapy. J. Natl. Cancer Inst. 2015 107 8 djv146 10.1093/jnci/djv146 26105028
    [Google Scholar]
  128. Mace T.A. Shakya R. Pitarresi J.R. Swanson B. McQuinn C.W. Loftus S. Nordquist E. Cruz-Monserrate Z. Yu L. Young G. Zhong X. Zimmers T.A. Ostrowski M.C. Ludwig T. Bloomston M. Bekaii-Saab T. Lesinski G.B. IL-6 and PD-L1 antibody blockade combination therapy reduces tumour progression in murine models of pancreatic cancer. Gut 2018 67 2 320 332 10.1136/gutjnl‑2016‑311585 27797936
    [Google Scholar]
  129. Soares K.C. Rucki A.A. Wu A.A. Olino K. Xiao Q. Chai Y. Wamwea A. Bigelow E. Lutz E. Liu L. Yao S. Anders R.A. Laheru D. Wolfgang C.L. Edil B.H. Schulick R.D. Jaffee E.M. Zheng L. PD-1/PD-L1 blockade together with vaccine therapy facilitates effector T-cell infiltration into pancreatic tumors. J. Immunother. 2015 38 1 1 11 10.1097/CJI.0000000000000062 25415283
    [Google Scholar]
  130. Luheshi N.M. Coates-Ulrichsen J. Harper J. Mullins S. Sulikowski M.G. Martin P. Brown L. Lewis A. Davies G. Morrow M. Wilkinson R.W. Transformation of the tumour microenvironment by a CD40 agonist antibody correlates with improved responses to PD-L1 blockade in a mouse orthotopic pancreatic tumour model. Oncotarget 2016 7 14 18508 18520 10.18632/oncotarget.7610 26918344
    [Google Scholar]
  131. Mehla K. Tremayne J. Grunkemeyer J.A. O’Connell K.A. Steele M.M. Caffrey T.C. Zhu X. Yu F. Singh P.K. Schultes B.C. Madiyalakan R. Nicodemus C.F. Hollingsworth M.A. Combination of mAb-AR20.5, anti-PD-L1 and PolyICLC inhibits tumor progression and prolongs survival of MUC1.Tg mice challenged with pancreatic tumors. Cancer Immunol. Immunother. 2018 67 3 445 457 10.1007/s00262‑017‑2095‑7 29204701
    [Google Scholar]
  132. Winograd R. Byrne K.T. Evans R.A. Odorizzi P.M. Meyer A.R.L. Bajor D.L. Clendenin C. Stanger B.Z. Furth E.E. Wherry E.J. Vonderheide R.H. Induction of T-cell immunity overcomes complete resistance to PD-1 and CTLA-4 blockade and improves survival in pancreatic carcinoma. Cancer Immunol. Res. 2015 3 4 399 411 10.1158/2326‑6066.CIR‑14‑0215 25678581
    [Google Scholar]
  133. van Herk E.H. te Velde A.A. Treg subsets in inflammatory bowel disease and colorectal carcinoma: Characteristics, role, and therapeutic targets. J. Gastroenterol. Hepatol. 2016 31 8 1393 1404 10.1111/jgh.13342 26990130
    [Google Scholar]
  134. Collison L.W. Pillai M.R. Chaturvedi V. Vignali D.A.A. Regulatory T cell suppression is potentiated by target T cells in a cell contact, IL-35- and IL-10-dependent manner. J. Immunol. 2009 182 10 6121 6128 10.4049/jimmunol.0803646 19414764
    [Google Scholar]
  135. Olguín J.E. Medina-Andrade I. Rodríguez T. Rodríguez-Sosa M. Terrazas L.I. Relevance of Regulatory T Cells during Colorectal Cancer Development. Cancers (Basel) 2020 12 7 1888 10.3390/cancers12071888 32674255
    [Google Scholar]
  136. Damo M. Joshi N.S. Treg cell IL-10 and IL-35 exhaust CD8+ T cells in tumors. Nat. Immunol. 2019 20 6 674 675 10.1038/s41590‑019‑0389‑y 31011189
    [Google Scholar]
  137. Nakamura K. Kitani A. Fuss I. Pedersen A. Harada N. Nawata H. Strober W. TGF-beta 1 plays an important role in the mechanism of CD4+CD25+ regulatory T cell activity in both humans and mice. J. Immunol. 2004 172 2 834 842 10.4049/jimmunol.172.2.834 14707053
    [Google Scholar]
  138. Maj T. Wang W. Crespo J. Zhang H. Wang W. Wei S. Zhao L. Vatan L. Shao I. Szeliga W. Lyssiotis C. Liu J.R. Kryczek I. Zou W. Oxidative stress controls regulatory T cell apoptosis and suppressor activity and PD-L1-blockade resistance in tumor. Nat. Immunol. 2017 18 12 1332 1341 10.1038/ni.3868 29083399
    [Google Scholar]
  139. Cao X. Cai S.F. Fehniger T.A. Song J. Collins L.I. Piwnica-Worms D.R. Ley T.J. Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance. Immunity 2007 27 4 635 646 10.1016/j.immuni.2007.08.014 17919943
    [Google Scholar]
  140. Grossman W.J. Verbsky J.W. Barchet W. Colonna M. Atkinson J.P. Ley T.J. Human T regulatory cells can use the perforin pathway to cause autologous target cell death. Immunity 2004 21 4 589 601 10.1016/j.immuni.2004.09.002 15485635
    [Google Scholar]
  141. Rodriguez P.C. Quiceno D.G. Zabaleta J. Ortiz B. Zea A.H. Piazuelo M.B. Delgado A. Correa P. Brayer J. Sotomayor E.M. Antonia S. Ochoa J.B. Ochoa A.C. Arginase I production in the tumor microenvironment by mature myeloid cells inhibits T-cell receptor expression and antigen-specific T-cell responses. Cancer Res. 2004 64 16 5839 5849 10.1158/0008‑5472.CAN‑04‑0465 15313928
    [Google Scholar]
  142. Barbera-Guillem E. Nyhus J.K. Wolford C.C. Friece C.R. Sampsel J.W. Vascular endothelial growth factor secretion by tumor-infiltrating macrophages essentially supports tumor angiogenesis, and IgG immune complexes potentiate the process. Cancer Res. 2002 62 23 7042 7049 12460925
    [Google Scholar]
  143. Phinney B.B. Ray A.L. Peretti A.S. Jerman S.J. Grim C. Pinchuk I.V. Beswick E.J. MK2 Regulates Macrophage Chemokine Activity and Recruitment to Promote Colon Tumor Growth. Front. Immunol. 2018 9 1857 10.3389/fimmu.2018.01857 30298062
    [Google Scholar]
  144. Ham I.H. Lee D. Hur H. Role of Cancer-Associated Fibroblast in Gastric Cancer Progression and Resistance to Treatments. J. Oncol. 2019 2019 1 11 10.1155/2019/6270784 31281359
    [Google Scholar]
  145. Kato T. Noma K. Ohara T. Kashima H. Katsura Y. Sato H. Komoto S. Katsube R. Ninomiya T. Tazawa H. Shirakawa Y. Fujiwara T. Cancer-Associated Fibroblasts Affect Intratumoral CD8+ and FoxP3+ T Cells Via IL6 in the Tumor Microenvironment. Clin. Cancer Res. 2018 24 19 4820 4833 10.1158/1078‑0432.CCR‑18‑0205 29921731
    [Google Scholar]
  146. Ashique S. Bhowmick M. Pal R. Khatoon H. Kumar P. Sharma H. Multi drug resistance in colorectal cancer-approaches to overcome, advancements and future success. Advances Cancer Biol-Metast 2024 10 100114
    [Google Scholar]
  147. Ashique S. Garg A. Hussain A. Farid A. Kumar P. Taghizadeh-Hesary F. Nanodelivery systems: An efficient and target‐specific approach for drug‐resistant cancers. Cancer Med. 2023 12 18 18797 18825 10.1002/cam4.6502 37668041
    [Google Scholar]
  148. D’Souza W.N. Chang C.F. Fischer A.M. Li M. Hedrick S.M. The Erk2 MAPK regulates CD8 T cell proliferation and survival. J. Immunol. 2008 181 11 7617 7629 10.4049/jimmunol.181.11.7617 19017950
    [Google Scholar]
  149. Yang J. Yan J. Liu B. Targeting VEGF/VEGFR to Modulate Antitumor Immunity. Front. Immunol. 2018 9 978 10.3389/fimmu.2018.00978 29774034
    [Google Scholar]
  150. Liu Z. Lv J. Dang Q. Liu L. Weng S. Wang L. Zhou Z. Kong Y. Li H. Han Y. Han X. Engineering neoantigen vaccines to improve cancer personalized immunotherapy. Int. J. Biol. Sci. 2022 18 15 5607 5623 10.7150/ijbs.76281 36263174
    [Google Scholar]
  151. Fukuhara H. Ino Y. Todo T. Oncolytic virus therapy: A new era of cancer treatment at dawn. Cancer Sci. 2016 107 10 1373 1379 10.1111/cas.13027 27486853
    [Google Scholar]
  152. Ge Y. Wang X. Guo Y. Yan J. Abuduwaili A. Aximujiang K. Yan J. Wu M. Gut microbiota influence tumor development and Alter interactions with the human immune system. J. Exp. Clin. Cancer Res. 2021 40 1 42 10.1186/s13046‑021‑01845‑6
    [Google Scholar]
  153. Duffy M.J. Crown J. Biomarkers for predicting response to immunotherapy with immune checkpoint inhibitors in cancer patients. Clin. Chem. 2019 65 10 1228 1238 10.1373/clinchem.2019.303644 31315901
    [Google Scholar]
  154. Xu Z. Wang X. Zeng S. Ren X. Yan Y. Gong Z. Applying artificial intelligence for cancer immunotherapy. Acta Pharm. Sin. B 2021 11 11 3393 3405 10.1016/j.apsb.2021.02.007 34900525
    [Google Scholar]
  155. Khalili-Tanha G. Mohit R. Asadnia A. Khazaei M. Dashtiahangar M. Maftooh M. Nassiri M. Hassanian S.M. Ghayour-Mobarhan M. Kiani M.A. Ferns G.A. Batra J. Nazari E. Avan A. Identification of ZMYND19 as a novel biomarker of colorectal cancer: RNA-sequencing and machine learning analysis. J. Cell Commun. Signal. 2023 17 4 1469 1485 10.1007/s12079‑023‑00779‑2 37428302
    [Google Scholar]
  156. Le D.T. Uram J.N. Wang H. Bartlett B.R. Kemberling H. Eyring A.D. Skora A.D. Luber B.S. Azad N.S. Laheru D. Biedrzycki B. Donehower R.C. Zaheer A. Fisher G.A. Crocenzi T.S. Lee J.J. Duffy S.M. Goldberg R.M. de la Chapelle A. Koshiji M. Bhaijee F. Huebner T. Hruban R.H. Wood L.D. Cuka N. Pardoll D.M. Papadopoulos N. Kinzler K.W. Zhou S. Cornish T.C. Taube J.M. Anders R.A. Eshleman J.R. Vogelstein B. Diaz L.A. Jr PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N. Engl. J. Med. 2015 372 26 2509 2520 10.1056/NEJMoa1500596 26028255
    [Google Scholar]
  157. Overman M.J. McDermott R. Leach J.L. Lonardi S. Lenz H.J. Morse M.A. Desai J. Hill A. Axelson M. Moss R.A. Goldberg M.V. Cao Z.A. Ledeine J.M. Maglinte G.A. Kopetz S. André T. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): An open-label, multicentre, phase 2 study. Lancet Oncol. 2017 18 9 1182 1191 10.1016/S1470‑2045(17)30422‑9 28734759
    [Google Scholar]
  158. Bendell J.C. Powderly J.D. Lieu C.H. Eckhardt S.G. Hurwitz H. Hochster H.S. Safety and efficacy of MPDL3280A (anti-PDL1) in combination with bevacizumab (bev) and/or FOLFOX in patients (pts) with metastatic colorectal cancer (mCRC). American Soc Clin Oncol 2015 33 3 704 10.1200/jco.2015.33.3_suppl.704
    [Google Scholar]
  159. Bendell J.C. Kim T.W. Goh B.C. Wallin J. Oh D-Y. Han S-W. Clinical activity and safety of cobimetinib (cobi) and atezolizumab in colorectal cancer (CRC). American Soc Clin Oncol 2016 35 15 3502 10.1200/JCO.2016.34.15_suppl.3502
    [Google Scholar]
  160. Fuchs CS Doi T Jang RW Muro K Satoh T Machado M Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer: Phase 2 clinical KEYNOTE-059 trial. JAMA Oncol 20186 4 5 e180013-e
    [Google Scholar]
  161. Shitara K. Özgüroğlu M. Bang Y.J. Di Bartolomeo M. Mandalà M. Ryu M.H. Fornaro L. Olesiński T. Caglevic C. Chung H.C. Muro K. Goekkurt E. Mansoor W. McDermott R.S. Shacham-Shmueli E. Chen X. Mayo C. Kang S.P. Ohtsu A. Fuchs C.S. Lerzo G. O’Connor J.M. Mendez G.A. Lynam J. Tebbutt N. Wong M. Strickland A. Karapetis C. Goldstein D. Vasey P. Van Laethem J-L. Van Cutsem E. Berry S. Vincent M. Muller B. Rey F. Zambrano A. Guerra J. Krogh M. Baeksgaard L. Yilmaz M. Elme A. Magi A. Auvinen P. Alanko T. Moehler M. Kunzmann V. Seufferlein T. Thuss-Patience P. Goekkurt E. Hoehler T. Haag G. Al-Batran S-E. Castro H. Lopez K. Aguilar Vasquez M. Sandoval M. Lam K.O. Cuffe S. Kelly C. Geva R. Shacham-Shmueli E. Hubert A. Beny A. Brenner B. Giuseppe A. Falcone A. Maiello E. Passalacqua R. Montesarchio V. Hara H. Chin K. Nishina T. Komatsu Y. Machida N. Hironaka S. Satoh T. Tamura T. Sugimoto N. Cho H. Omuro Y. Kato K. Goto M. Hyodo I. Yoshida K. Baba H. Esaki T. Furuse J. Wan Mohammed W.Z. Hernandez Hernandez C. Casas Garcia J. Dominguez Andrade A. Clarke K. Hjortland G. Glenjen N. Kubiatowski T. Jacek J. Wojtukiewicz M. Lazarev S. Lancukhay Y. Afanasayev S. Moiseyenko V. Kostorov V. Protsenko S. Shirinkin V. Sakaeva D. Fadeeva N. Yong W.P. Ng C.H.M. Robertson B. Rapaport B. Cohen G. Dreosti L. Ruff P. Jacobs C. Landers G. Szpak W. Roh S-Y. Lee J. Kim Y.H. Bang Y-J. Chung H.C. Ryu M-H. Alsina Maqueda M. Longo Munoz F. Cervantes Aguilar A. Aranda Aguilar E. Garcia Alfonso P. Rivera F. Feliu Batle J. Pazo Cid R. Yeh K-H. Chen J-S. Chao Y. Yen C-J. Özgüroğlu M. Kara O. Yalcin S. Hochhauser D. Chau I. Benson A. Shankaran V. Shaib W. Philip P. Sharma V. Siegel R. Sun W. Wainberg Z. George B. Bullock A. Myrick S. Faruol J. Siegel R. Larson T. Becerra C. Ratnam S. Richards D.A. Riche S.L. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): A randomised, open-label, controlled, phase 3 trial. Lancet 2018 392 10142 123 133 10.1016/S0140‑6736(18)31257‑1 29880231
    [Google Scholar]
  162. Lote H. Cafferkey C. Chau I. PD-1 and PD-L1 blockade in gastrointestinal malignancies. Cancer Treat. Rev. 2015 41 10 893 903 10.1016/j.ctrv.2015.09.004 26412280
    [Google Scholar]
  163. Boku N. Ryu M.H. Kato K. Chung H.C. Minashi K. Lee K.W. Cho H. Kang W.K. Komatsu Y. Tsuda M. Yamaguchi K. Hara H. Fumita S. Azuma M. Chen L.T. Kang Y.K. Safety and efficacy of nivolumab in combination with S-1/capecitabine plus oxaliplatin in patients with previously untreated, unresectable, advanced, or recurrent gastric/gastroesophageal junction cancer: Interim results of a randomized, phase II trial (ATTRACTION-4). Ann. Oncol. 2019 30 2 250 258 10.1093/annonc/mdy540 30566590
    [Google Scholar]
  164. Janjigian Y.Y. Bendell J. Calvo E. Kim J.W. Ascierto P.A. Sharma P. Ott P.A. Peltola K. Jaeger D. Evans J. de Braud F. Chau I. Harbison C.T. Dorange C. Tschaika M. Le D.T. CheckMate-032 study: Efficacy and safety of nivolumab and nivolumab plus ipilimumab in patients with metastatic esophagogastric cancer. J. Clin. Oncol. 2018 36 28 2836 2844 10.1200/JCO.2017.76.6212 30110194
    [Google Scholar]
  165. Bang Y.J. Ruiz E.Y. Van Cutsem E. Lee K.W. Wyrwicz L. Schenker M. Alsina M. Ryu M.H. Chung H.C. Evesque L. Al-Batran S.E. Park S.H. Lichinitser M. Boku N. Moehler M.H. Hong J. Xiong H. Hallwachs R. Conti I. Taieb J. Phase III, randomised trial of avelumab versus physician’s choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: Primary analysis of JAVELIN Gastric 300. Ann. Oncol. 2018 29 10 2052 2060 10.1093/annonc/mdy264 30052729
    [Google Scholar]
  166. Le D.T. Lutz E. Uram J.N. Sugar E.A. Onners B. Solt S. Evaluation of ipilimumab in combination with allogeneic pancreatic tumor cells transfected with a GM-CSF gene in previously treated pancreatic cancer. J Immunother 2013 36 7 382 9 10.1097/CJI.0b013e31829fb7a2
    [Google Scholar]
  167. Aglietta M. Barone C. Sawyer M.B. Moore M.J. Miller W.H. Jr Bagalà C. Colombi F. Cagnazzo C. Gioeni L. Wang E. Huang B. Fly K.D. Leone F. A phase I dose escalation trial of tremelimumab (CP-675,206) in combination with gemcitabine in chemotherapy-naive patients with metastatic pancreatic cancer. Ann. Oncol. 2014 25 9 1750 1755 10.1093/annonc/mdu205 24907635
    [Google Scholar]
  168. Kalyan A. Kircher S.M. Mohindra N.A. Nimeiri H.S. Maurer V. Rademaker A. Ipilimumab and gemcitabine for advanced pancreas cancer: A phase Ib study. American Soc Clin Oncol 2016 34 15 15747
    [Google Scholar]
  169. Friedlander M. Meniawy T. Markman B. Mileshkin L.R. Harnett P.R. Millward M. Lundy J. Freimund A.E. Norris C. Mu S. Wu J. Paton V.E. Wang L. Gao B. A phase 1b study of the anti-PD-1 monoclonal antibody BGB-A317 (A317) in combination with the PARP inhibitor BGB-290 (290) in advanced solid tumors. J. Clin. Oncol. 2017 35 15_suppl Suppl. 3013 10.1200/JCO.2017.35.15_suppl.3013
    [Google Scholar]
  170. Weiss G.J. Blaydorn L. Beck J. Bornemann-Kolatzki K. Urnovitz H. Schütz E. Khemka V. Phase Ib/II study of gemcitabine, nab-paclitaxel, and pembrolizumab in metastatic pancreatic adenocarcinoma. Invest. New Drugs 2018 36 1 96 102 10.1007/s10637‑017‑0525‑1 29119276
    [Google Scholar]
  171. Wainberg Z.A. Hochster H.S. George B. Gutierrez M. Johns M.E. Chiorean E.G. Phase I study of nivolumab (nivo)+ nab-paclitaxel (nab-P)±gemcitabine (Gem) in solid tumors: Interim results from the pancreatic cancer (PC) cohorts. American Soc Clin Oncol 2017 35 4 412
    [Google Scholar]
  172. Katz M.H. Varadhachary G.R. Bauer T.W. Acquavella N. Merchant N.B. Le T.M. Preliminary safety data from a randomized multicenter phase Ib/II study of neoadjuvant chemoradiation therapy (CRT) alone or in combination with pembrolizumab in patients with resectable or borderline resectable pancreatic cancer. American Soc Clin Oncol 2017 35 15 4125 10.1200/JCO.2017.35.15_suppl.4125
    [Google Scholar]
  173. Fujiwara Y Shitara K Shimizu T Yonemori K Matsubara N Ohno I Abstract A204: INCB024360 (Epacadostat) monotherapy and in combination with pembrolizumab in patients with advanced solid tumors: Primary results from first-in-Japanese phase I study (KEYNOTE-434). Mol Cancer Therapeut. 2018 17 1_Suppl A204-A
    [Google Scholar]
  174. Strauss J. Heery C.R. Schlom J. Madan R.A. Cao L. Kang Z. Lamping E. Marté J.L. Donahue R.N. Grenga I. Cordes L. Christensen O. Mahnke L. Helwig C. Gulley J.L. Phase I trial of M7824 (MSB0011359C), a bifunctional fusion protein targeting PD-L1 and TGFβ, in advanced solid tumors. Clin. Cancer Res. 2018 24 6 1287 1295 10.1158/1078‑0432.CCR‑17‑2653 29298798
    [Google Scholar]
  175. O’Reilly E.M. Oh D-Y. Dhani N. Renouf D.J. Lee M.A. Sun W. A randomized phase 2 study of durvalumab monotherapy and in combination with tremelimumab in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC): ALPS study. American Soc Clin Oncol 2018 36 4 217 10.1200/JCO.2018.36.4_suppl.217
    [Google Scholar]
  176. Renouf D.J. Dhani N.C. Kavan P. Jonker D.J. Wei A.C-c. Hsu T. The Canadian Cancer Trials Group PA. 7 trial: Results from the safety run in of a randomized phase II study of gemcitabine (GEM) and nab-paclitaxel (Nab-P) versus GEM, nab-P, durvalumab (D), and tremelimumab (T) as first-line therapy in metastatic pancreatic ductal adenocarcinoma (mPDAC). American Soc Clin Oncol 2018 36 4 349
    [Google Scholar]
  177. Kojima T. Shah M.A. Muro K. Francois E. Adenis A. Hsu C.H. Doi T. Moriwaki T. Kim S.B. Lee S.H. Bennouna J. Kato K. Shen L. Enzinger P. Qin S.K. Ferreira P. Chen J. Girotto G. de la Fouchardiere C. Senellart H. Al-Rajabi R. Lordick F. Wang R. Suryawanshi S. Bhagia P. Kang S.P. Metges J.P. Randomized phase III KEYNOTE-181 study of pembrolizumab versus chemotherapy in advanced esophageal cancer. J. Clin. Oncol. 2020 38 35 4138 4148 10.1200/JCO.20.01888 33026938
    [Google Scholar]
  178. Zhang B. Qi L. Wang X. Xu J. Liu Y. Mu L. Wang X. Bai L. Huang J. Phase II clinical trial using camrelizumab combined with apatinib and chemotherapy as the first‐line treatment of advanced esophageal squamous cell carcinoma. Cancer Commun. (Lond.) 2020 40 12 711 720 10.1002/cac2.12119 33314747
    [Google Scholar]
  179. Fujiwara Y. Iguchi H. Yamamoto N. Hayama M. Nii M. Ueda S. Komuro K. Sugimoto M. Vlahovic G. Kozuki T. Tolerability and efficacy of durvalumab in Japanese patients with advanced solid tumors. Cancer Sci. 2019 110 5 1715 1723 10.1111/cas.14003 30891877
    [Google Scholar]
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The Therapeutic Potential of Targeting Tumor Microenvironment and Modulation of Immunotherapy in Gastrointestinal Cancer
Bentham Science Publishers ; https://doi.org/10.2174/0115680096319027240820055043
/content/journals/ccdt/10.2174/0115680096319027240820055043
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  • Article Type:     Review Article
Keywords: chimeric antigen receptor T-cell ; immune checkpoint inhibitors ; tumor microenvironment ; Immunotherapy ; gastrointestinal cancer ; drug resistance

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