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image of Revolutionizing Glioblastoma Immunotherapy Conquering Transport and Biological Challenges, Innovating Combinatorial Approaches for Unprecedented Treatment Success

Abstract

Glioblastomas are the most common primary brain cancer and present many challenges in treatment, with the current standard-of-care treatments yielding a median survival rate of less than 15 months. While immunotherapy against cancer has been very effective in some cancers, its application in glioblastoma has been limited so far. The following review touches upon some of the critical challenges associated with successful immunotherapy in glioblastoma, covering transport-related obstacles presented by the blood-brain barrier, biological complexity within the central nervous system, and the interplay between glioblastoma and immune cells. Ongoing clinical trials testing the efficacy of different immunotherapeutic strategies, including immune checkpoint blockade, vaccination, and adoptive cell transfer, are discussed. These strategies are inherently challenged by the low immunogenicity of glioblastoma, the unique immune-protective mechanisms of the immune system within the CNS, and the predominant features of the immune-suppressive tumor microenvironment. Current therapeutic modalities reviewed include surgical resection, radiation therapy, and temozolomide-based chemotherapy, with discussions on new forms of approaches to enhance immune activation: vaccines, oncolytic viruses, and adoptive cell therapies such as CAR T cells and NK cells. The perpetual problem of resistance to immunotherapy underlines the need for combination strategies and precise testing within advanced and animal tumor models, considering the large variability in glioblastomas.

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2024-11-11
2025-04-23

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References

  1. Ostrom Q.T. Gittleman H. Liao P. Vecchione-Koval T. Wolinsky Y. Kruchko C. Barnholtz-Sloan J.S. CBTRUS Statistical Report: Primary brain and other central nervous system tumors diagnosed in the United States in 2010–2014. Neuro-oncol. 2017 19 Suppl. 5 v1 v88 10.1093/neuonc/nox158 29117289
    [Google Scholar]
  2. Darvin P. Toor S.M. Sasidharan Nair V. Elkord E. Immune checkpoint inhibitors: recent progress and potential biomarkers. Exp. Mol. Med. 2018 50 12 1 11 10.1038/s12276‑018‑0191‑1 30546008
    [Google Scholar]
  3. Roberts Z.J. Better M. Bot A. Roberts M.R. Ribas A. Axicabtagene ciloleucel, a first-in-class CAR T cell therapy for aggressive NHL. Leuk. Lymphoma 2018 59 8 1785 1796 10.1080/10428194.2017.1387905 29058502
    [Google Scholar]
  4. Rosic G. Selakovic D. Omarova S. Cancer signaling, cell/gene therapy, diagnosis and role of nanobiomaterials. Advances in Biology & Earth Sciences 2024 9 Special Issue 11 34 10.62476/abes9s11
    [Google Scholar]
  5. Xu J. Biosynthesis, characterization, and investigation of antimicrobial and cytotoxic activities of silver nanoparticles using Solanum tuberosum peel aqueous extract. Heliyon 2023 9 8
    [Google Scholar]
  6. İpek P. Green synthesis and evaluation of antipathogenic, antioxidant, and anticholinesterase activities of gold nanoparticles (Au NPs) from Allium cepa L. peel aqueous extract. Biomass Conv. Bioref. 2024 14 9 10661 10670
    [Google Scholar]
  7. Sarkaria J.N. Hu L.S. Parney I.F. Pafundi D.H. Brinkmann D.H. Laack N.N. Giannini C. Burns T.C. Kizilbash S.H. Laramy J.K. Swanson K.R. Kaufmann T.J. Brown P.D. Agar N.Y.R. Galanis E. Buckner J.C. Elmquist W.F. Is the blood–brain barrier really disrupted in all glioblastomas? A critical assessment of existing clinical data. Neuro-oncol. 2018 20 2 184 191 10.1093/neuonc/nox175 29016900
    [Google Scholar]
  8. Jain R.K. Stylianopoulos T. Delivering nanomedicine to solid tumors. Nat. Rev. Clin. Oncol. 2010 7 11 653 664 10.1038/nrclinonc.2010.139 20838415
    [Google Scholar]
  9. Hashizume H. Baluk P. Morikawa S. McLean J.W. Thurston G. Roberge S. Jain R.K. McDonald D.M. Openings between defective endothelial cells explain tumor vessel leakiness. Am. J. Pathol. 2000 156 4 1363 1380 10.1016/S0002‑9440(10)65006‑7 10751361
    [Google Scholar]
  10. Peer D. Karp J.M. Hong S. Farokhzad O.C. Margalit R. Langer R. Nanocarriers as an emerging platform for cancer therapy. Nat. Nanotechnol. 2007 2 12 751 760 10.1038/nnano.2007.387 18654426
    [Google Scholar]
  11. Danhier F. To exploit the tumor microenvironment: Since the EPR effect fails in the clinic, what is the future of nanomedicine? J. Control. Release 2016 244 Pt A 108 121 10.1016/j.jconrel.2016.11.015 27871992
    [Google Scholar]
  12. Hansen A.E. Petersen A.L. Henriksen J.R. Boerresen B. Rasmussen P. Elema D.R. RosenschöldPMa, Kristensen AT, Kjær A, Andresen TL. Positron emission tomography based elucidation of the enhanced permeability and retention efect in dogs with cancer using copper-64 liposomes. ACS Nano 2015 9 6985 6995 10.1021/acsnano.5b01324 26022907
    [Google Scholar]
  13. Sindhwani S. Syed A.M. Ngai J. Kingston B.R. Maiorino L. Rothschild J. MacMillan P. Zhang Y. Rajesh N.U. Hoang T. Wu J.L.Y. Wilhelm S. Zilman A. Gadde S. Sulaiman A. Ouyang B. Lin Z. Wang L. Egeblad M. Chan W.C.W. The entry of nanoparticles into solid tumours. Nat. Mater. 2020 19 5 566 575 10.1038/s41563‑019‑0566‑2 31932672
    [Google Scholar]
  14. Hodi F.S. O’Day S.J. McDermott D.F. Weber R.W. Sosman J.A. Haanen J.B. Gonzalez R. Robert C. Schadendorf D. Hassel J.C. Akerley W. van den Eertwegh A.J.M. Lutzky J. Lorigan P. Vaubel J.M. Linette G.P. Hogg D. Ottensmeier C.H. Lebbé C. Peschel C. Quirt I. Clark J.I. Wolchok J.D. Weber J.S. Tian J. Yellin M.J. Nichol G.M. Hoos A. Urba W.J. Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med. 2010 363 8 711 723 10.1056/NEJMoa1003466 20525992
    [Google Scholar]
  15. Subhan M.A. Parveen F. Filipczak N. Yalamarty S.S.K. Torchilin V.P. Approaches to improve EPR-based drug delivery for cancer therapy and diagnosis. J. Pers. Med. 2023 13 3 389 10.3390/jpm13030389 36983571
    [Google Scholar]
  16. Tian Y. Cheng T. Sun F. Zhou Y. Yuan C. Guo Z. Wang Z. Effect of biophysical properties of tumor extracellular matrix on intratumoral fate of nanoparticles: Implications on the design of nanomedicine. Adv. Colloid Interface Sci. 2024 326 103124 10.1016/j.cis.2024.103124 38461766
    [Google Scholar]
  17. Tran V.L. Lux F. Tournier N. Jego B. Maître X. Anisorac M. Comtat C. Jan S. Selmeczi K. Evans M.J. Tillement O. Kuhnast B. Truillet C. Quantitative tissue pharmacokinetics and EPR effect of AGuIX nanoparticles: a multimodal imaging study in an orthotopic glioblastoma rat model and healthy macaque. Adv. Healthc. Mater. 2021 10 16 2100656 10.1002/adhm.202100656 34212539
    [Google Scholar]
  18. Rustenhoven J. Kipnis J. Bypassing the blood-brain barrier. Science 2019 366 6472 1448 1449 10.1126/science.aay0479 31857468
    [Google Scholar]
  19. Rutledge W.C. Kong J. Gao J. Gutman D.A. Cooper L.A.D. Appin C. Park Y. Scarpace L. Mikkelsen T. Cohen M.L. Aldape K.D. McLendon R.E. Lehman N.L. Miller C.R. Schniederjan M.J. Brennan C.W. Saltz J.H. Moreno C.S. Brat D.J. Tumor-infiltrating lymphocytes in glioblastoma are associated with specific genomic alterations and related to transcriptional class. Clin. Cancer Res. 2013 19 18 4951 4960 10.1158/1078‑0432.CCR‑13‑0551 23864165
    [Google Scholar]
  20. Yeung J.T. Hamilton R.L. Ohnishi K. Ikeura M. Potter D.M. Nikiforova M.N. Ferrone S. Jakacki R.I. Pollack I.F. Okada H. LOH in the HLA class I region at 6p21 is associated with shorter survival in newly diagnosed adult glioblastoma. Clin. Cancer Res. 2013 19 7 1816 1826 10.1158/1078‑0432.CCR‑12‑2861 23401227
    [Google Scholar]
  21. Grossman S.A. Ye X. Lesser G. Sloan A. Carraway H. Desideri S. Piantadosi S. Consortium N.C. Immunosuppression in patients with high-grade gliomas treated with radiation and temozolomide. Clin. Cancer Res. 2011 17 16 5473 5480 10.1158/1078‑0432.CCR‑11‑0774 21737504
    [Google Scholar]
  22. Mazor G. Levin L. Picard D. Ahmadov U. Carén H. Borkhardt A. Reifenberger G. Leprivier G. Remke M. Rotblat B. The lncRNA TP73-AS1 is linked to aggressiveness in glioblastoma and promotes temozolomide resistance in glioblastoma cancer stem cells. Cell Death Dis. 2019 10 3 246 10.1038/s41419‑019‑1477‑5 30867410
    [Google Scholar]
  23. Orzan F. De Bacco F. Crisafulli G. Pellegatta S. Mussolin B. Siravegna G. D’Ambrosio A. Comoglio P.M. Finocchiaro G. Boccaccio C. Genetic evolution of glioblastoma stem-like cells from primary to recurrent tumor. Stem Cells 2017 35 11 2218 2228 10.1002/stem.2703 28895245
    [Google Scholar]
  24. Guha-Thakurta N. Wierda W.G. Cerebral edema secondary to chimeric antigen receptor T-cell immunotherapy. Neurology 2018 91 18 843 10.1212/WNL.0000000000006436 30373920
    [Google Scholar]
  25. Tran T.T. Jilaveanu L.B. Omuro A. Chiang V.L. Huttner A. Kluger H.M. Complications associated with immunotherapy for brain metastases. Curr. Opin. Neurol. 2019 32 6 907 916 10.1097/WCO.0000000000000756 31577604
    [Google Scholar]
  26. Young R.M. Jamshidi A. Davis G. Sherman J.H. Current trends in the surgical management and treatment of adult glioblastoma. Ann. Transl. Med. 2015 3 9 121 26207249
    [Google Scholar]
  27. Brown T.J. Brennan M.C. Li M. Church E.W. Brandmeir N.J. Rakszawski K.L. Patel A.S. Rizk E.B. Suki D. Sawaya R. Glantz M. Association of the Extent of Resection With Survival in Glioblastoma. JAMA Oncol. 2016 2 11 1460 1469 10.1001/jamaoncol.2016.1373 27310651
    [Google Scholar]
  28. Han Q. Liang H. Cheng P. Yang H. Zhao P. Gross Total vs. Subtotal Resection on Survival Outcomes in Elderly Patients With High-Grade Glioma: A Systematic Review and Meta-Analysis. Front. Oncol. 2020 10 151 10.3389/fonc.2020.00151 32257941
    [Google Scholar]
  29. Tunthanathip T. Madteng S. Factors associated with the extent of resection of glioblastoma. Precis. Cancer Med. 2020 3 12 10.21037/pcm.2020.01.01
    [Google Scholar]
  30. 14. Mann, J.; Ramakrishna, R.; Magge, R.; Wernicke, A.G. Advances in radiotherapy for glioblastoma. Front. Neurol. 2017 8 748 [CrossRef] [PubMed]
    [Google Scholar]
  31. Cabrera A.R. Kirkpatrick J.P. Fiveash J.B. Shih H.A. Koay E.J. Lutz S. Petit J. Chao S.T. Brown P.D. Vogelbaum M. Reardon D.A. Chakravarti A. Wen P.Y. Chang E. Radiation therapy for glioblastoma: Executive summary of an American Society for Radiation Oncology Evidence-Based Clinical Practice Guideline. Pract. Radiat. Oncol. 2016 6 4 217 225 10.1016/j.prro.2016.03.007 27211230
    [Google Scholar]
  32. Nabors L.B. Portnow J. Ammirati M. Baehring J. Brem H. Butowski N. Fenstermaker R.A. Forsyth P. Hattangadi-Gluth J. Holdhoff M. Howard S. Junck L. Kaley T. Kumthekar P. Loeffler J.S. Moots P.L. Mrugala M.M. Nagpal S. Pandey M. Parney I. Peters K. Puduvalli V.K. Ragsdale J. III Rockhill J. Rogers L. Rusthoven C. Shonka N. Shrieve D.C. Sills A.K. Jr Swinnen L.J. Tsien C. Weiss S. Wen P.Y. Willmarth N. Bergman M.A. Engh A. NCCN guidelines insights: Central nervous system cancers, version 1. J. Natl. Compr. Canc. Netw. 2017 15 11 1331 1345 10.6004/jnccn.2017.0166 29118226
    [Google Scholar]
  33. Graeber M.B. Scheithauer B.W. Kreutzberg G.W. Microglia in brain tumors. Glia 2002 40 2 252 259 10.1002/glia.10147 12379912
    [Google Scholar]
  34. Reardon D.A. Freeman G. Wu C. Chiocca E.A. Wucherpfennig K.W. Wen P.Y. Fritsch E.F. Curry W.T. Jr Sampson J.H. Dranoff G. Immunotherapy advances for glioblastoma. Neuro-oncol. 2014 16 11 1441 1458 10.1093/neuonc/nou212 25190673
    [Google Scholar]
  35. Reardon D.A. Brandes A.A. Omuro A. Mulholland P. Lim M. Wick A. Baehring J. Ahluwalia M.S. Roth P. Bähr O. Phuphanich S. Sepulveda J.M. De Souza P. Sahebjam S. Carleton M. Tatsuoka K. Taitt C. Zwirtes R. Sampson J. Weller M. Effect of nivolumab vs bevacizumab in patients with recurrent glioblastoma: The checkmate 143 phase 3 randomized clinical trial. JAMA Oncol. 2020 6 7 1003 1010 10.1001/jamaoncol.2020.1024 32437507
    [Google Scholar]
  36. Ray A. Manjila S. Hdeib A.M. Radhakrishnan A. Nock C.J. Cohen M.L. Sloan A. Extracranial metastasis of gliobastoma: Three illustrative cases and current review of the molecular pathology and management strategies. Mol. Clin. Oncol. 2015 3 3 479 486 10.3892/mco.2015.494 26137254
    [Google Scholar]
  37. Rosen J. Blau T. Grau S.J. Barbe M.T. Fink G.R. Galldiks N. Extracranial metastases of a cerebral glioblastoma: A case report and review of the literature. Case Rep. Oncol. 2018 11 2 591 600 10.1159/000492111 30283316
    [Google Scholar]
  38. Rossi J. Giaccherini L. Cavallieri F. Napoli M. Moratti C. Froio E. Serra S. Fraternali A. Ghadirpour R. Cozzi S. Ciammella P. Iaccarino C. Pascarella R. Valzania F. Pisanello A. Extracranial metastases in secondary glioblastoma multiforme: a case report. BMC Neurol. 2020 20 1 382 10.1186/s12883‑020‑01959‑y 33087049
    [Google Scholar]
  39. Colli L.M. Machiela M.J. Myers T.A. Jessop L. Yu K. Chanock S.J. Burden of nonsynonymous mutations among tcga cancers and candidate immune checkpoint inhibitor responses. Cancer Res. 2016 76 13 3767 3772 10.1158/0008‑5472.CAN‑16‑0170 27197178
    [Google Scholar]
  40. Weenink B. Draaisma K. Ooi H.Z. Kros J.M. Sillevis Smitt P.A.E. Debets R. French P.J. Low-grade glioma harbors few CD8 T cells, which is accompanied by decreased expression of chemo-attractants, not immunogenic antigens. Sci. Rep. 2019 9 1 14643 10.1038/s41598‑019‑51063‑6 31601888
    [Google Scholar]
  41. Keskin D.B. Anandappa A.J. Sun J. Tirosh I. Mathewson N.D. Li S. Oliveira G. Giobbie-Hurder A. Felt K. Gjini E. Shukla S.A. Hu Z. Li L. Le P.M. Allesøe R.L. Richman A.R. Kowalczyk M.S. Abdelrahman S. Geduldig J.E. Charbonneau S. Pelton K. Iorgulescu J.B. Elagina L. Zhang W. Olive O. McCluskey C. Olsen L.R. Stevens J. Lane W.J. Salazar A.M. Daley H. Wen P.Y. Chiocca E.A. Harden M. Lennon N.J. Gabriel S. Getz G. Lander E.S. Regev A. Ritz J. Neuberg D. Rodig S.J. Ligon K.L. Suvà M.L. Wucherpfennig K.W. Hacohen N. Fritsch E.F. Livak K.J. Ott P.A. Wu C.J. Reardon D.A. Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Nature 2019 565 7738 234 239 10.1038/s41586‑018‑0792‑9 30568305
    [Google Scholar]
  42. Dutoit V. Migliorini D. Dietrich P.Y. Walker P.R. Immunotherapy of malignant tumors in the brain: How different from other sites? Front. Oncol. 2016 6 256 10.3389/fonc.2016.00256 28003994
    [Google Scholar]
  43. Shraibman B. Barnea E. Kadosh D.M. Haimovich Y. Slobodin G. Rosner I. López-Larrea C. Hilf N. Kuttruff S. Song C. Britten C. Castle J. Kreiter S. Frenzel K. Tatagiba M. Tabatabai G. Dietrich P.Y. Dutoit V. Wick W. Platten M. Winkler F. von Deimling A. Kroep J. Sahuquillo J. Martinez-Ricarte F. Rodon J. Lassen U. Ottensmeier C. van der Burg S.H. Thor Straten P. Poulsen H.S. Ponsati B. Okada H. Rammensee H.G. Sahin U. Singh H. Admon A. Identification of tumor antigens among the hla peptidomes of glioblastoma tumors and plasma. Mol. Cell. Proteomics 2019 18 6 1255 1268 10.1074/mcp.RA119.001524 31154438
    [Google Scholar]
  44. Facoetti A. Nano R. Zelini P. Morbini P. Benericetti E. Ceroni M. Campoli M. Ferrone S. Human leukocyte antigen and antigen processing machinery component defects in astrocytic tumors. Clin. Cancer Res. 2005 11 23 8304 8311 10.1158/1078‑0432.CCR‑04‑2588 16322289
    [Google Scholar]
  45. Schumacher T. Bunse L. Pusch S. Sahm F. Wiestler B. Quandt J. Menn O. Osswald M. Oezen I. Ott M. Keil M. Balß J. Rauschenbach K. Grabowska A.K. Vogler I. Diekmann J. Trautwein N. Eichmüller S.B. Okun J. Stevanović S. Riemer A.B. Sahin U. Friese M.A. Beckhove P. von Deimling A. Wick W. Platten M. A vaccine targeting mutant IDH1 induces antitumour immunity. Nature 2014 512 7514 324 327 10.1038/nature13387 25043048
    [Google Scholar]
  46. Ratnam N.M. Gilbert M.R. Giles A.J. Immunotherapy in CNS cancers: the role of immune cell trafficking. Neuro-oncol. 2019 21 1 37 46 10.1093/neuonc/noy084 29771386
    [Google Scholar]
  47. Yin J. Valin K.L. Dixon M.L. Leavenworth J.W. The role of microglia and macrophages in cns homeostasis, autoimmunity, and cancer. J. Immunol. Res. 2017 2017 1 12 10.1155/2017/5150678 29410971
    [Google Scholar]
  48. Orrego E. Castaneda C.A. Castillo M. Bernabe L.A. Casavilca S. Chakravarti A. Meng W. Garcia-Corrochano P. Villa-Robles M.R. Zevallos R. Mejia O. Deza P. Belmar-Lopez C. Ojeda L. Distribution of tumor-infiltrating immune cells in glioblastoma. CNS Oncol. 2018 7 4 CNS21 10.2217/cns‑2017‑0037 30299157
    [Google Scholar]
  49. Eckerdt F. Platanias L.C. Emerging role of glioma stem cells in mechanisms of therapy resistance. Cancers (Basel) 2023 15 13 3458 10.3390/cancers15133458 37444568
    [Google Scholar]
  50. Gupta A. Dwivedi T. A simplified overview of World Health Organization classification update of central nervous system tumors 2016. J. Neurosci. Rural Pract. 2017 8 4 629 641 10.4103/jnrp.jnrp_168_17 29204027
    [Google Scholar]
  51. Rayati M. Mansouri V. Ahmadbeigi N. Gene therapy in glioblastoma multiforme: Can it be a role changer? Heliyon 2024 10 5 e27087 10.1016/j.heliyon.2024.e27087 38439834
    [Google Scholar]
  52. DeCordova S. Shastri A. Tsolaki A.G. Yasmin H. Klein L. Singh S.K. Kishore U. Molecular heterogeneity and immunosuppressive microenvironment in glioblastoma. Front. Immunol. 2020 11 1402 10.3389/fimmu.2020.01402 32765498
    [Google Scholar]
  53. Varn F.S. Wang Y. Mullins D.W. Fiering S. Cheng C. Systematic pan-cancer analysis reveals immune cell interactions in the tumor microenvironment. Cancer Res. 2017 77 6 1271 1282 10.1158/0008‑5472.CAN‑16‑2490 28126714
    [Google Scholar]
  54. Yang I. Tihan T. Han S.J. Wrensch M.R. Wiencke J. Sughrue M.E. Parsa A.T. CD8+ T-cell infiltrate in newly diagnosed glioblastoma is associated with long-term survival. J. Clin. Neurosci. 2010 17 11 1381 1385 10.1016/j.jocn.2010.03.031 20727764
    [Google Scholar]
  55. Mostafa H. Pala A. Högel J. Hlavac M. Dietrich E. Westhoff M.A. Nonnenmacher L. Burster T. Georgieff M. Wirtz C.R. Schneider E.M. Immune phenotypes predict survival in patients with glioblastoma multiforme. J. Hematol. Oncol. 2016 9 1 77 10.1186/s13045‑016‑0272‑3 27585656
    [Google Scholar]
  56. Groblewska M. Litman-Zawadzka A. Mroczko B. The role of selected chemokines and their receptors in the development of gliomas. Int. J. Mol. Sci. 2020 21 10 3704 10.3390/ijms21103704 32456359
    [Google Scholar]
  57. Zhang J. Caruso F.P. Sa J.K. Justesen S. Nam D.H. Sims P. Ceccarelli M. Lasorella A. Iavarone A. The combination of neoantigen quality and T lymphocyte infiltrates identifies glioblastomas with the longest survival. Commun. Biol. 2019 2 1 135 10.1038/s42003‑019‑0369‑7 31044160
    [Google Scholar]
  58. Platten M. Ochs K. Lemke D. Opitz C. Wick W. Microenvironmental clues for glioma immunotherapy. Curr. Neurol. Neurosci. Rep. 2014 14 4 440 10.1007/s11910‑014‑0440‑1 24604058
    [Google Scholar]
  59. Broekman M.L. Maas S.L.N. Abels E.R. Mempel T.R. Krichevsky A.M. Breakefield X.O. Multidimensional communication in the microenvirons of glioblastoma. Nat. Rev. Neurol. 2018 14 8 482 495 10.1038/s41582‑018‑0025‑8 29985475
    [Google Scholar]
  60. Quail D.F. Joyce J.A. The microenvironmental landscape of brain tumors. Cancer Cell 2017 31 3 326 341 10.1016/j.ccell.2017.02.009 28292436
    [Google Scholar]
  61. Roy L.O. Poirier M.B. Fortin D. Transforming growth factor-beta and its implication in the malignancy of gliomas. Target. Oncol. 2015 10 1 1 14 10.1007/s11523‑014‑0308‑y 24590691
    [Google Scholar]
  62. Frei K. Gramatzki D. Tritschler I. Schroeder J.J. Espinoza L. Rushing E.J. Weller M. Transforming growth factor-β pathway activity in glioblastoma. Oncotarget 2015 6 8 5963 5977 10.18632/oncotarget.3467 25849941
    [Google Scholar]
  63. Hazrati A. Soudi S. Malekpour K. Mahmoudi M. Rahimi A. Hashemi S.M. Varma R.S. Immune cells-derived exosomes function as a double-edged sword: role in disease progression and their therapeutic applications. Biomark. Res. 2022 10 1 30 10.1186/s40364‑022‑00374‑4 35550636
    [Google Scholar]
  64. Lohr J. Ratliff T. Huppertz A. Ge Y. Dictus C. Ahmadi R. Grau S. Hiraoka N. Eckstein V. Ecker R.C. Korff T. von Deimling A. Unterberg A. Beckhove P. Herold-Mende C. Effector T-cell infiltration positively impacts survival of glioblastoma patients and is impaired by tumor-derived TGF-β. Clin. Cancer Res. 2011 17 13 4296 4308 10.1158/1078‑0432.CCR‑10‑2557 21478334
    [Google Scholar]
  65. Platten M. Weller M. Wick W. Shaping the glioma immune microenvironment through tryptophan metabolism. CNS Oncol. 2012 1 1 99 106 10.2217/cns.12.6 25054303
    [Google Scholar]
  66. Piccirillo C.A. Letterio J.J. Thornton A.M. McHugh R.S. Mamura M. Mizuhara H. Shevach E.M. CD4(+)CD25(+) regulatory T cells can mediate suppressor function in the absence of transforming growth factor β1 production and responsiveness. J. Exp. Med. 2002 196 2 237 246 10.1084/jem.20020590 12119348
    [Google Scholar]
  67. Munn D.H. Mellor A.L. Indoleamine 2,3-dioxygenase and tumor-induced tolerance. J. Clin. Invest. 2007 117 5 1147 1154 10.1172/JCI31178 17476344
    [Google Scholar]
  68. Dunn G.P. Cloughesy T.F. Maus M.V. Prins R.M. Reardon D.A. Sonabend A.M. Emerging immunotherapies for malignant glioma: from immunogenomics to cell therapy. Neuro-oncol. 2020 22 10 1425 1438 10.1093/neuonc/noaa154 32615600
    [Google Scholar]
  69. Sampson J.H. Heimberger A.B. Archer G.E. Aldape K.D. Friedman A.H. Friedman H.S. Gilbert M.R. Herndon J.E. II McLendon R.E. Mitchell D.A. Reardon D.A. Sawaya R. Schmittling R.J. Shi W. Vredenburgh J.J. Bigner D.D. Immunologic escape after prolonged progression-free survival with epidermal growth factor receptor variant III peptide vaccination in patients with newly diagnosed glioblastoma. J. Clin. Oncol. 2010 28 31 4722 4729 10.1200/JCO.2010.28.6963 20921459
    [Google Scholar]
  70. Lynes J.P. Nwankwo A.K. Sur H.P. Sanchez V.E. Sarpong K.A. Ariyo O.I. Dominah G.A. Nduom E.K. Biomarkers for immunotherapy for treatment of glioblastoma. J. Immunother. Cancer 2020 8 1 e000348 10.1136/jitc‑2019‑000348 32474411
    [Google Scholar]
  71. Weller M. Butowski N. Tran D.D. Recht L.D. Lim M. Hirte H. Ashby L. Mechtler L. Goldlust S.A. Iwamoto F. Drappatz J. O’Rourke D.M. Wong M. Hamilton M.G. Finocchiaro G. Perry J. Wick W. Green J. He Y. Turner C.D. Yellin M.J. Keler T. Davis T.A. Stupp R. Sampson J.H. Butowski N. Campian J. Recht L. Lim M. Ashby L. Drappatz J. Hirte H. Iwamoto F. Mechtler L. Goldlust S. Becker K. Barnett G. Nicholas G. Desjardins A. Benkers T. Wagle N. Groves M. Kesari S. Horvath Z. Merrell R. Curry R. O’Rourke J. Schuster D. Wong M. Mrugala M. Jensen R. Trusheim J. Lesser G. Belanger K. Sloan A. Purow B. Fink K. Raizer J. Schulder M. Nair S. Peak S. Perry J. Brandes A. Weller M. Mohile N. Landolfi J. Olson J. Finocchiaro G. Jennens R. DeSouza P. Robinson B. Crittenden M. Shih K. Flowers A. Ong S. Connelly J. Hadjipanayis C. Giglio P. Mott F. Mathieu D. Lessard N. Sepulveda S.J. Lövey J. Wheeler H. Inglis P-L. Hardie C. Bota D. Lesniak M. Portnow J. Frankel B. Junck L. Thompson R. Berk L. McGhie J. Macdonald D. Saran F. Soffietti R. Blumenthal D. André de S.B.C.M. Nowak A. Singhal N. Hottinger A. Schmid A. Srkalovic G. Baskin D. Fadul C. Nabors L. LaRocca R. Villano J. Paleologos N. Kavan P. Pitz M. Thiessen B. Idbaih A. Frenel J.S. Domont J. Grauer O. Hau P. Marosi C. Sroubek J. Hovey E. Sridhar P.S. Cher L. Dunbar E. Coyle T. Raymond J. Barton K. Guarino M. Raval S. Stea B. Dietrich J. Hopkins K. Erridge S. Steinbach J-P. Pineda L.E. Balana Q.C. Sonia del B.B. Wenczl M. Molnár K. Hideghéty K. Lossos A. Myra van L. Levy A. Harrup R. Patterson W. Lwin Z. Sathornsumetee S. Lee E-J. Ho J-T. Emmons S. Duic J.P. Shao S. Ashamalla H. Weaver M. Lutzky J. Avgeropoulos N. Hanna W. Nadipuram M. Cecchi G. O’Donnell R. Pannullo S. Carney J. Hamilton M. MacNeil M. Beaney R. Fabbro M. Schnell O. Fietkau R. Stockhammer G. Malinova B. Odrazka K. Sames M. Miguel Gil G. Razis E. Lavrenkov K. Castro G. Ramirez F. Baldotto C. Viola F. Malheiros S. Lickliter J. Gauden S. Dechaphunkul A. Thaipisuttikul I. Thotathil Z. Ma H-I. Cheng W-Y. Chang C-H. Salas F. Dietrich P-Y. Mamot C. Nayak L. Nag S. Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): A randomised, double-blind, international phase 3 trial. Lancet Oncol. 2017 18 10 1373 1385 10.1016/S1470‑2045(17)30517‑X 28844499
    [Google Scholar]
  72. Lim M. Xia Y. Bettegowda C. Weller M. Current state of immunotherapy for glioblastoma. Nat. Rev. Clin. Oncol. 2018 15 7 422 442 10.1038/s41571‑018‑0003‑5 29643471
    [Google Scholar]
  73. Suryadevara C.M. Desai R. Abel M.L. Riccione K.A. Batich K.A. Shen S.H. Chongsathidkiet P. Gedeon P.C. Elsamadicy A.A. Snyder D.J. Herndon J.E. II Healy P. Archer G.E. Choi B.D. Fecci P.E. Sampson J.H. Sanchez-Perez L. Temozolomide lymphodepletion enhances CAR abundance and correlates with antitumor efficacy against established glioblastoma. OncoImmunology 2018 7 6 e1434464 10.1080/2162402X.2018.1434464 29872570
    [Google Scholar]
  74. Do A.S.M.S. Amano T. Edwards L.A. Zhang L. De Peralta-Venturina M. Yu J.S. CD133 mRNA-loaded dendritic cell vaccination abrogates glioma stem cell propagation in humanized glioblastoma mouse model. Mol. Ther. Oncolytics 2020 18 295 303 10.1016/j.omto.2020.06.019 32728617
    [Google Scholar]
  75. Liau L.M. Ashkan K. Tran D.D. Campian J.L. Trusheim J.E. Cobbs C.S. Heth J.A. Salacz M. Taylor S. D’Andre S.D. First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma. J. Transl. Med. 2018 16 1
    [Google Scholar]
  76. Eoli M. Corbetta C. Anghileri E. Di Ianni N. Milani M. Cuccarini V. Musio S. Paterra R. Frigerio S. Nava S. Lisini D. Pessina S. Maddaloni L. Lombardi R. Tardini M. Ferroli P. DiMeco F. Bruzzone M.G. Antozzi C. Pollo B. Finocchiaro G. Pellegatta S. Expansion of effector and memory T cells is associated with increased survival in recurrent glioblastomas treated with dendritic cell immunotherapy. Neurooncol. Adv. 2019 1 1 vdz022 10.1093/noajnl/vdz022 32642658
    [Google Scholar]
  77. Russell S.J. Peng K.W. Bell J.C. Oncolytic virotherapy. Nat. Biotechnol. 2012 30 7 658 670 10.1038/nbt.2287 22781695
    [Google Scholar]
  78. Martikainen M. Essand M. Virus-based immunotherapy of glioblastoma. Cancers (Basel) 2019 11 2 186 10.3390/cancers11020186 30764570
    [Google Scholar]
  79. Jiang H. Rivera-Molina Y. Gomez-Manzano C. Clise-Dwyer K. Bover L. Vence L.M. Yuan Y. Lang F.F. Toniatti C. Hossain M.B. Fueyo J. Oncolytic adenovirus and tumor-targeting immune modulatory therapy improve autologous cancer vaccination. Cancer Res. 2017 77 14 3894 3907 10.1158/0008‑5472.CAN‑17‑0468 28566332
    [Google Scholar]
  80. Salinas R.D. Durgin J.S. O’Rourke D.M. Potential of glioblastoma-targeted chimeric antigen receptor (CAR) T-cell therapy. CNS Drugs 2020 34 2 127 145 10.1007/s40263‑019‑00687‑3 31916100
    [Google Scholar]
  81. Diefenbach A. Raulet D.H. The innate immune response to tumors and its role in the induction of T‐cell immunity. Immunol. Rev. 2002 188 1 9 21 10.1034/j.1600‑065X.2002.18802.x 12445277
    [Google Scholar]
  82. O’Rourke D.M. Nasrallah M.P. Desai A. Melenhorst J.J. Mansfield K. Morrissette J.J.D. Martinez-Lage M. Brem S. Maloney E. Shen A. Isaacs R. Mohan S. Plesa G. Lacey S.F. Navenot J.M. Zheng Z. Levine B.L. Okada H. June C.H. Brogdon J.L. Maus M.V. A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma. Sci. Transl. Med. 2017 9 399 eaaa0984 10.1126/scitranslmed.aaa0984 28724573
    [Google Scholar]
  83. Choi B.D. Yu X. Castano A.P. Bouffard A.A. Schmidts A. Larson R.C. Bailey S.R. Boroughs A.C. Frigault M.J. Leick M.B. Scarfò I. Cetrulo C.L. Demehri S. Nahed B.V. Cahill D.P. Wakimoto H. Curry W.T. Carter B.S. Maus M.V. CAR-T cells secreting BiTEs circumvent antigen escape without detectable toxicity. Nat. Biotechnol. 2019 37 9 1049 1058 10.1038/s41587‑019‑0192‑1 31332324
    [Google Scholar]
  84. Medikonda R. Dunn G. Rahman M. Fecci P. Lim M. A review of glioblastoma immunotherapy. J. Neurooncol. 2021 151 1 41 53 10.1007/s11060‑020‑03448‑1 32253714
    [Google Scholar]
  85. Marusyk A. Polyak K. Tumor heterogeneity: Causes and consequences. Biochim. Biophys. Acta 2010 1805 1 105 117 19931353
    [Google Scholar]
  86. Klein E. Hau A.C. Oudin A. Golebiewska A. Niclou S.P. Glioblastoma organoids: Pre-clinical applications and challenges in the context of immunotherapy. Front. Oncol. 2020 10 604121 10.3389/fonc.2020.604121 33364198
    [Google Scholar]
  87. Goodspeed A. Heiser L.M. Gray J.W. Costello J.C. Tumor-derived cell lines as molecular models of cancer pharmacogenomics. Mol. Cancer Res. 2016 14 1 3 13 10.1158/1541‑7786.MCR‑15‑0189 26248648
    [Google Scholar]
  88. Lee J. Kotliarova S. Kotliarov Y. Li A. Su Q. Donin N.M. Pastorino S. Purow B.W. Christopher N. Zhang W. Park J.K. Fine H.A. Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines. Cancer Cell 2006 9 5 391 403 10.1016/j.ccr.2006.03.030 16697959
    [Google Scholar]
  89. Kaur K. Topchyan P. Kozlowska A.K. Ohanian N. Chiang J. Maung P.O. Park S.H. Ko M.W. Fang C. Nishimura I. Jewett A. Super-charged NK cells inhibit growth and progression of stem-like/poorly differentiated oral tumors in vivo in humanized BLT mice; effect on tumor differentiation and response to chemotherapeutic drugs. OncoImmunology 2018 7 5 e1426518 10.1080/2162402X.2018.1426518 29721395
    [Google Scholar]
  90. Merz F. Gaunitz F. Dehghani F. Renner C. Meixensberger J. Gutenberg A. Giese A. Schopow K. Hellwig C. Schäfer M. Bauer M. Stöcker H. Taucher-Scholz G. Durante M. Bechmann I. Organotypic slice cultures of human glioblastoma reveal different susceptibilities to treatments. Neuro-oncol. 2013 15 6 670 681 10.1093/neuonc/not003 23576601
    [Google Scholar]
  91. Parker J.J. Lizarraga M. Waziri A. Foshay K.M. A human glioblastoma organotypic slice culture model for study of tumor cell migration and patient-specific effects of anti-invasive drugs. J. Vis. Exp. 2017 2017 125 53557 28784966
    [Google Scholar]
  92. Hubert C.G. Rivera M. Spangler L.C. Wu Q. Mack S.C. Prager B.C. Couce M. McLendon R.E. Sloan A.E. Rich J.N. A three-dimensional organoid culture system derived from human glioblastomas recapitulates the hypoxic gradients and cancer stem cell heterogeneity of tumors found in vivo. Cancer Res. 2016 76 8 2465 2477 10.1158/0008‑5472.CAN‑15‑2402 26896279
    [Google Scholar]
  93. Jacob F. Salinas R.D. Zhang D.Y. Nguyen P.T.T. Schnoll J.G. Wong S.Z.H. Thokala R. Sheikh S. Saxena D. Prokop S. Liu D. Qian X. Petrov D. Lucas T. Chen H.I. Dorsey J.F. Christian K.M. Binder Z.A. Nasrallah M. Brem S. O’Rourke D.M. Ming G. Song H. A patient-derived glioblastoma organoid model and biobank recapitulates inter- and intra-tumoral heterogeneity. Cell 2020 180 1 188 204.e22 10.1016/j.cell.2019.11.036 31883794
    [Google Scholar]
  94. Olson B. Li Y. Lin Y. Liu E.T. Patnaik A. Mouse models for cancer immunotherapy research. Cancer Discov. 2018 8 11 1358 1365 10.1158/2159‑8290.CD‑18‑0044 30309862
    [Google Scholar]
  95. Louis D.N. Molecular pathology of malignant gliomas. Annu. Rev. Pathol. 2006 1 1 97 117 10.1146/annurev.pathol.1.110304.100043 18039109
    [Google Scholar]
  96. Rich J.N. Cancer stem cells in radiation resistance. Cancer Res. 2007 67 19 8980 8984 10.1158/0008‑5472.CAN‑07‑0895 17908997
    [Google Scholar]
  97. Zhao Y. Shuen T.W.H. Toh T.B. Chan X.Y. Liu M. Tan S.Y. Fan Y. Yang H. Lyer S.G. Bonney G.K. Loh E. Chang K.T.E. Tan T.C. Zhai W. Chan J.K.Y. Chow E.K.H. Chee C.E. Lee G.H. Dan Y.Y. Chow P.K.H. Toh H.C. Lim S.G. Chen Q. Development of a new patient-derived xenograft humanised mouse model to study human-specific tumour microenvironment and immunotherapy. Gut 2018 67 10 1845 1854 10.1136/gutjnl‑2017‑315201 29602780
    [Google Scholar]
  98. Lin S. Huang G. Cheng L. Li Z. Xiao Y. Deng Q. Jiang Y. Li B. Lin S. Wang S. Wu Q. Yao H. Cao S. Li Y. Liu P. Wei W. Pei D. Yao Y. Wen Z. Zhang X. Wu Y. Zhang Z. Cui S. Sun X. Qian X. Li P. Establishment of peripheral blood mononuclear cell-derived humanized lung cancer mouse models for studying efficacy of PD-L1/PD-1 targeted immunotherapy. MAbs 2018 10 8 1301 1311 10.1080/19420862.2018.1518948 30204048
    [Google Scholar]
  99. Bao S. Wu Q. McLendon R.E. Hao Y. Shi Q. Hjelmeland A.B. Dewhirst M.W. Bigner D.D. Rich J.N. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 2006 444 7120 756 760 10.1038/nature05236 17051156
    [Google Scholar]
  100. Haddad A.F. Young J.S. Amara D. Berger M.S. Raleigh D.R. Aghi M.K. Butowski N.A. Mouse models of glioblastoma for the evaluation of novel therapeutic strategies. Neurooncol. Adv. 2021 3 1 vdab100 10.1093/noajnl/vdab100 34466804
    [Google Scholar]
  101. Parker N.R. Khong P. Parkinson J.F. Howell V.M. Wheeler H.R. Molecular heterogeneity in glioblastoma: Potential clinical implications. Front. Oncol. 2015 5 55 10.3389/fonc.2015.00055 25785247
    [Google Scholar]
  102. Conklin K.A. Chemotherapy-associated oxidative stress: Impact on chemotherapeutic effectiveness. Integr. Cancer Ther. 2004 3 4 294 300 10.1177/1534735404270335 15523100
    [Google Scholar]
  103. Wo J.Y. Viswanathan A.N. Impact of radiotherapy on fertility, pregnancy, and neonatal outcomes in female cancer patients. Int. J. Radiat. Oncol. Biol. Phys. 2009 73 5 1304 1312 10.1016/j.ijrobp.2008.12.016
    [Google Scholar]
  104. Balachandran V.P. Beatty G.L. Dougan S.K. Broadening the impact of immunotherapy to pancreatic cancer: challenges and opportunities. Gastroenterology 2019 156 7 2056 2072 10.1053/j.gastro.2018.12.038 30660727
    [Google Scholar]
  105. Le Rhun E. Preusser M. Roth P. Reardon D.A. van den Bent M. Wen P. Reifenberger G. Weller M. Molecular targeted therapy of glioblastoma. Cancer Treat. Rev. 2019 80 101896 10.1016/j.ctrv.2019.101896 31541850
    [Google Scholar]
  106. Wang T. Shigdar S. Gantier M.P. Hou Y. Wang L. Li Y. Shamaileh H.A. Yin W. Zhou S.F. Zhao X. Duan W. Cancer stem cell targeted therapy: progress amid controversies. Oncotarget 2015 6 42 44191 44206 10.18632/oncotarget.6176 26496035
    [Google Scholar]
  107. Shergalis A. Bankhead A. III Luesakul U. Muangsin N. Neamati N. Current challenges and opportunities in treating glioblastoma. Pharmacol. Rev. 2018 70 3 412 445 10.1124/pr.117.014944 29669750
    [Google Scholar]
  108. Belden C.J. Valdes P.A. Ran C. Pastel D.A. Harris B.T. Fadul C.E. Israel M.A. Paulsen K. Roberts D.W. Genetics of glioblastoma: a window into its imaging and histopathologic variability. Radiographics 2011 31 6 1717 1740 10.1148/rg.316115512 21997991
    [Google Scholar]
  109. Schiffer D. Annovazzi L. Casalone C. Corona C. Mellai M. Glioblastoma: microenvironment and niche concept. Cancers (Basel) 2018 11 1 5 10.3390/cancers11010005 30577488
    [Google Scholar]
  110. Lathia J.D. Mack S.C. Mulkearns-Hubert E.E. Valentim C.L.L. Rich J.N. Cancer stem cells in glioblastoma. Genes Dev. 2015 29 12 1203 1217 10.1101/gad.261982.115 26109046
    [Google Scholar]
  111. Razavi S.M. Lee K.E. Jin B.E. Aujla P.S. Gholamin S. Li G. Immune evasion strategies of glioblastoma. Front. Surg. 2016 3 11 10.3389/fsurg.2016.00011 26973839
    [Google Scholar]
  112. Desai K. Hubben A. Ahluwalia M. The role of checkpoint inhibitors in glioblastoma. Target. Oncol. 2019 14 4 375 394 10.1007/s11523‑019‑00655‑3 31290002
    [Google Scholar]
  113. Martínez Bedoya D. Dutoit V. Migliorini D. Allogeneic CAR T cells: an alternative to overcome challenges of CAR T cell therapy in glioblastoma. Front. Immunol. 2021 12 640082 10.3389/fimmu.2021.640082 33746981
    [Google Scholar]
  114. Taylor T.E. Furnari F.B. Cavenee W.K. Targeting EGFR for treatment of glioblastoma: molecular basis to overcome resistance. Curr. Cancer Drug Targets 2012 12 3 197 209 10.2174/156800912799277557 22268382
    [Google Scholar]
  115. Garnier D. Meehan B. Kislinger T. Daniel P. Sinha A. Abdulkarim B. Nakano I. Rak J. Divergent evolution of temozolomide resistance in glioblastoma stem cells is reflected in extracellular vesicles and coupled with radiosensitization. Neuro-oncol. 2018 20 2 236 248 10.1093/neuonc/nox142 29016925
    [Google Scholar]
  116. Doucette T. Rao G. Rao A. Shen L. Aldape K. Wei J. Dziurzynski K. Gilbert M. Heimberger A.B. Immune heterogeneity of glioblastoma subtypes: extrapolation from the cancer genome atlas. Cancer Immunol. Res. 2013 1 2 112 122 10.1158/2326‑6066.CIR‑13‑0028 24409449
    [Google Scholar]
  117. Wang Q. Hu B. Hu X. Kim H. Squatrito M. Scarpace L. deCarvalho A.C. Lyu S. Li P. Li Y. Barthel F. Cho H.J. Lin Y.H. Satani N. Martinez-Ledesma E. Zheng S. Chang E. Sauvé C.E.G. Olar A. Lan Z.D. Finocchiaro G. Phillips J.J. Berger M.S. Gabrusiewicz K.R. Wang G. Eskilsson E. Hu J. Mikkelsen T. DePinho R.A. Muller F. Heimberger A.B. Sulman E.P. Nam D.H. Verhaak R.G.W. Tumor evolution of glioma-intrinsic gene expression subtypes associates with immunological changes in the microenvironment. Cancer Cell 2017 32 1 42 56.e6 10.1016/j.ccell.2017.06.003 28697342
    [Google Scholar]
  118. Azzarelli R. Organoid models of glioblastoma to study brain tumor stem cells. Front. Cell Dev. Biol. 2020 8 220 10.3389/fcell.2020.00220 32373607
    [Google Scholar]
  119. Bar E.E. Glioblastoma, cancer stem cells and hypoxia. Brain Pathol. 2011 21 2 119 129 10.1111/j.1750‑3639.2010.00460.x 21054626
    [Google Scholar]
  120. Tang X. Zhang S. Fu R. Zhang L. Huang K. Peng H. Dai L. Chen Q. Therapeutic prospects of mRNA-based gene therapy for glioblastoma. Front. Oncol. 2019 9 1208 10.3389/fonc.2019.01208 31781503
    [Google Scholar]
  121. Chen J. Li Y. Yu T.S. McKay R.M. Burns D.K. Kernie S.G. Parada L.F. A restricted cell population propagates glioblastoma growth after chemotherapy. Nature 2012 488 7412 522 526 10.1038/nature11287 22854781
    [Google Scholar]
  122. Oh H.C. Shim J.K. Park J. Lee J.H. Choi R.J. Kim N.H. Kim H.S. Moon J.H. Kim E.H. Chang J.H. Yook J.I. Kang S.G. Combined effects of niclosamide and temozolomide against human glioblastoma tumorspheres. J. Cancer Res. Clin. Oncol. 2020 146 11 2817 2828 10.1007/s00432‑020‑03330‑7 32712753
    [Google Scholar]
  123. Xie X.P. Laks D.R. Sun D. Ganbold M. Wang Z. Pedraza A.M. Bale T. Tabar V. Brennan C. Zhou X. Parada L.F. Quiescent human glioblastoma cancer stem cells drive tumor initiation, expansion, and recurrence following chemotherapy. Dev. Cell 2022 57 1 32 46.e8 10.1016/j.devcel.2021.12.007 35016005
    [Google Scholar]
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Revolutionizing Glioblastoma Immunotherapy Conquering Transport and Biological Challenges, Innovating Combinatorial Approaches for Unprecedented Treatment Success
Bentham Science Publishers ; https://doi.org/10.2174/012212697X332800241103174044
/content/journals/ccand/10.2174/012212697X332800241103174044
/content/journals/ccand/10.2174/012212697X332800241103174044
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  • Article Type:     Review Article
Keywords: natural killer (NK) cells ; T-lymphocytes cell ; Glioblastomas ; cancer immunotherapy ; immune system

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