Skip to content
2000
image of Transporter Associated with Antigen Processing Proteins (TAP-1 and TAP-2) Gene Expression of MHC-I Downregulated in Oral Squamous Carcinoma

Abstract

Background

TAP-1 and TAP-2 are crucial proteins for loading antigenic peptides after proteasome-mediated endogenous processing of the MHC-I (Major Histocompatibility Complex-I) pathway. Our study aimed to explore the Transporter Associated with Antigen Processing proteins (TAP-1 and TAP-2) in oral squamous cell carcinoma and premalignant oral lesions.

Methods

We recruited a total of 135 subjects from the outpatient department of the ENT unit of our institute. Real-time Polymerase Chain Reaction (PCR) was used to evaluate the levels of TAP-1 and TAP-2 gene expression in pre-cancerous and oral squamous carcinoma samples. Additionally, we measured the circulating levels of inflammatory markers using an automated biochemistry analyzer.

Results

In the current study, we found that the subjects with oral squamous cell carcinoma had lower expressions of the TAP 1 and TAP 2 genes than precancerous oral subjects of OSMF, leukoplakia, and OLP. In oral squamous carcinoma subjects, we found a 1.7- and 2.1-fold change in gene expression of TAP-1 and TAP-2, respectively, compared to control subjects. Furthermore, we observed an increase in levels of metabolic inflammatory biomarkers of CRP, ESR, and ferritin in oral squamous carcinoma subjects compared to premalignant cases and controls, indicating the presence and aggravation of systemic inflammation.

Conclusion

The study revealed that subjects with oral squamous cell carcinoma have lower TAP 1 and TAP 2 gene expression than premalignant control subjects, thus affecting MHC-I processing, which ultimately affects the functioning of the immune system. These results have the potential to improve our understanding of disease pathophysiology and provide more targeted treatment options.

This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Loading

Article metrics loading...

/content/journals/emiddt/10.2174/0118715303344715241225184322
2025-02-11
2025-07-14
The full text of this item is not currently available.

References

  1. Johnson D.E. Burtness B. Leemans C.R. Lui V.W.Y. Bauman J.E. Grandis J.R. Head and neck squamous cell carcinoma. Nat. Rev. Dis. Primers 2020 6 1 92 10.1038/s41572‑020‑00224‑3 33243986
    [Google Scholar]
  2. Bray F. Ferlay J. Soerjomataram I. Siegel R.L. Torre L.A. Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018 68 6 394 424 10.3322/caac.21492 30207593
    [Google Scholar]
  3. Sung H. Ferlay J. Siegel R.L. Laversanne M. Soerjomataram I. Jemal A. Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2021 71 3 209 249 10.3322/caac.21660 33538338
    [Google Scholar]
  4. Mishra A. Meherotra R. Head and neck cancer: Global burden and regional trends in India. Asian Pac. J. Cancer Prev. 2014 15 2 537 550 10.7314/APJCP.2014.15.2.537 24568456
    [Google Scholar]
  5. D’Cruz A.K. Vaish R. Dhar H. Oral cancers: Current status. Oral Oncol. 2018 87 64 69 10.1016/j.oraloncology.2018.10.013 30527245
    [Google Scholar]
  6. Sharma P. Saxena S. Aggarwal P. Trends in the epidemiology of oral squamous cell carcinoma in Western UP: An institutional study. Indian J. Dent. Res. 2010 21 3 316 319 10.4103/0970‑9290.70782 20930335
    [Google Scholar]
  7. Zhou Y. Tao L. Qiu J. Xu J. Yang X. Zhang Y. Tian X. Guan X. Cen X. Zhao Y. Tumor biomarkers for diagnosis, prognosis and targeted therapy. Signal Transduct. Target. Ther. 2024 9 1 132 10.1038/s41392‑024‑01823‑2 38763973
    [Google Scholar]
  8. Jiang X. Wu J. Wang J. Huang R. Tobacco and oral squamous cell carcinoma: A review of carcinogenic pathways. Tob. Induc. Dis. 2019 17 1 29 10.18332/tid/111652 31582940
    [Google Scholar]
  9. Sies H. Oxidative stress: A concept in redox biology and medicine. Redox Biol. 2015 4 180 183 10.1016/j.redox.2015.01.002 25588755
    [Google Scholar]
  10. Burgos-Molina A.M. Téllez Santana T. Redondo M. Bravo Romero M.J. The crucial role of inflammation and the immune system in colorectal cancer carcinogenesis: A comprehensive perspective. Int. J. Mol. Sci. 2024 25 11 6188 10.3390/ijms25116188 38892375
    [Google Scholar]
  11. Jack C.R. Jr Advances in Alzheimer’s disease research over the past two decades. Lancet Neurol. 2022 21 10 866 869 10.1016/S1474‑4422(22)00298‑8 36115352
    [Google Scholar]
  12. Greten F.R. Grivennikov S.I. Inflammation and cancer: Triggers, mechanisms, and consequences. Immunity 2019 51 1 27 41 10.1016/j.immuni.2019.06.025 31315034
    [Google Scholar]
  13. de Visser K.E. Joyce J.A. The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth. Cancer Cell 2023 41 3 374 403 10.1016/j.ccell.2023.02.016 36917948
    [Google Scholar]
  14. Dwivedi S. Purohit P. Sharma P. Single cell omics approach: A paradigm shift in diagnosis and therapy of cancer. Indian J. Clin. Biochem. 2019 34 1 1 2 10.1007/s12291‑019‑0812‑z 30728667
    [Google Scholar]
  15. Dwivedi S. Sharma P. Cancer stem cells: Future possibilities for cancer therapy. Indian J. Clin. Biochem. 2023 38 2 149 150 10.1007/s12291‑023‑01133‑4 37025432
    [Google Scholar]
  16. Dwivedi S. Purohit P. Misra R. Pareek P. Goel A. Khattri S. Pant K.K. Misra S. Sharma P. Diseases and molecular diagnostics: A step closer to precision medicine. Indian J. Clin. Biochem. 2017 32 4 374 398 10.1007/s12291‑017‑0688‑8 29062170
    [Google Scholar]
  17. Schambach A. Buchholz C.J. Torres-Ruiz R. Cichutek K. Morgan M. Trapani I. Büning H. A new age of precision gene therapy. Lancet 2024 403 10426 568 582 10.1016/S0140‑6736(23)01952‑9 38006899
    [Google Scholar]
  18. Dwivedi S. Purohit P. Vasudeva A. Kumar M. Agrawal R. Sheikh N.A. Chapter 9 - Gene therapy and gene editing in healthcare. Biotechnology in Healthcare. Barh D. Academic Press 2022 147 175 10.1016/B978‑0‑323‑89837‑9.00006‑1
    [Google Scholar]
  19. Li H. Yang Y. Hong W. Huang M. Wu M. Zhao X. Applications of genome editing technology in the targeted therapy of human diseases: Mechanisms, advances and prospects. Signal Transduct. Target. Ther. 2020 5 1 1 23 10.1038/s41392‑019‑0089‑y 32296011
    [Google Scholar]
  20. Birla M. Choudhary C. Singh G. Gupta S. Bhawana Vavilala P. The advent of nutrigenomics: A narrative review with an emphasis on psychological disorders. Prev. Nutr. Food Sci. 2022 27 2 150 164 10.3746/pnf.2022.27.2.150 35919568
    [Google Scholar]
  21. Sari G. Rock K.L. Tumor immune evasion through loss of MHC class-I antigen presentation. Curr. Opin. Immunol. 2023 83 102329 10.1016/j.coi.2023.102329 37130455
    [Google Scholar]
  22. Ukey S. Jain A. Dwivedi S. Vishnoi J.R. Chugh A. Purohit P. Pareek P. Elhence P. Misra S. Sharma P. Global and promoter specific hypermethylation of tumor suppressor genes P16, SOCS1, and SHP1 in oral squamous cell carcinoma and oral submucous fibrosis. J. Cancer Res. Ther. 2023 19 Suppl. 2 S551 S559 10.4103/jcrt.jcrt_689_22 38384018
    [Google Scholar]
  23. Mantel I. Sadiq B.A. Blander J.M. Spotlight on TAP and its vital role in antigen presentation and cross-presentation. Mol. Immunol. 2022 142 105 119 10.1016/j.molimm.2021.12.013 34973498
    [Google Scholar]
  24. Abele R. Tampé R. The ABCs of immunology: Structure and function of TAP, the transporter associated with antigen processing. Physiology 2004 19 4 216 224 10.1152/physiol.00002.2004 15304636
    [Google Scholar]
  25. Padariya M. Kote S. Mayordomo M. Dapic I. Alfaro J. Hupp T. Fahraeus R. Kalathiya U. Structural determinants of peptide-dependent TAP1-TAP2 transit passage targeted by viral proteins and altered by cancer-associated mutations. Comput. Struct. Biotechnol. J. 2021 19 5072 5091 10.1016/j.csbj.2021.09.006 34589184
    [Google Scholar]
  26. Taylor B.C. Balko J.M. Mechanisms of MHC-I downregulation and role in immunotherapy response. Front. Immunol. 2022 13 844866 10.3389/fimmu.2022.844866 35296095
    [Google Scholar]
  27. Ahmed H. Mahmud A.R. Siddiquee M.F.R. Shahriar A. Biswas P. Shimul M.E.K. Ahmed S.Z. Ema T.I. Rahman N. Khan M.A. Mizan M.F.R. Emran T.B. Role of T cells in cancer immunotherapy: Opportunities and challenges. Canc. Pathogen. Ther. 2023 1 2 116 126 10.1016/j.cpt.2022.12.002 38328405
    [Google Scholar]
  28. Raskov H. Orhan A. Christensen J.P. Gögenur I. Cytotoxic CD8+ T cells in cancer and cancer immunotherapy. Br. J. Cancer 2021 124 2 359 367 10.1038/s41416‑020‑01048‑4 32929195
    [Google Scholar]
  29. Zhao H. Wu L. Yan G. Chen Y. Zhou M. Wu Y. Li Y. Inflammation and tumor progression: Signaling pathways and targeted intervention. Signal Transduct. Target. Ther. 2021 6 1 263 10.1038/s41392‑021‑00658‑5 34248142
    [Google Scholar]
  30. Henle A.M. Nassar A. Puglisi-Knutson D. Youssef B. Knutson K.L. Downregulation of TAP1 and TAP2 in early stage breast cancer. PLoS One 2017 12 11 e0187323 10.1371/journal.pone.0187323 29091951
    [Google Scholar]
  31. Attaran N. Coates P. Zborayova K. Erdogan B. Magan M. Sgaramella N. Nylander K. Gu X. Antigen peptide transporters are upregulated in squamous cell carcinoma of the oral tongue and show sex‑specific associations with survival. Oncol. Lett. 2022 24 5 390 10.3892/ol.2022.13510 36276482
    [Google Scholar]
  32. Matsui M. Ikeda M. Akatsuka T. High expression of HLA-A2 on an oral squamous cell carcinoma with down-regulated transporter for antigen presentation. Biochem. Biophys. Res. Commun. 2001 280 4 1008 1014 10.1006/bbrc.2000.4234 11162627
    [Google Scholar]
  33. Shridhar K. Rajaraman P. Koyande S. Parikh P.M. Chaturvedi P. Dhillon P.K. Dikshit R.P. Trends in mouth cancer incidence in Mumbai, India (1995⿿2009): An age-period-cohort analysis. Cancer Epidemiol. 2016 42 66 71 10.1016/j.canep.2016.03.007 27043865
    [Google Scholar]
  34. Dwivedi S Purohit P Mittal Y Gupta G Goel A Verma R Chapter 22 - Genetic engineering: Towards gene therapy and molecular medicine. Omics Technologies and Bio-Engineering Academic Press 2018 507 532 10.1016/B978‑0‑12‑804659‑3.00022‑1
    [Google Scholar]
  35. Livak K.J. Schmittgen T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001 25 4 402 408 10.1006/meth.2001.1262 11846609
    [Google Scholar]
  36. Lehnert E. Tampé R. Structure and dynamics of antigenic peptides in complex with TAP. Front. Immunol. 2017 8 10 10.3389/fimmu.2017.00010 28194151
    [Google Scholar]
  37. Cassol-Spanemberg J. Rodríguez-de Rivera-Campillo M.E. Otero-Rey E.M. Estrugo-Devesa A. Jané-Salas E. López-López J. Oral lichen planus and its relationship with systemic diseases. A review of evidence. J. Clin. Exp. Dent. 2018 10 9 0 10.4317/jced.55145 30386529
    [Google Scholar]
  38. Tabassum A. Samdani M.N. Dhali T.C. Alam R. Ahammad F. Samad A. Karpiński T.M. Transporter associated with antigen processing 1 (TAP1) expression and prognostic analysis in breast, lung, liver, and ovarian cancer. J. Mol. Med. 2021 99 9 1293 1309 10.1007/s00109‑021‑02088‑w 34047812
    [Google Scholar]
  39. Dhatchinamoorthy K. Colbert J.D. Rock K.L. Cancer immune evasion through loss of MHC class I antigen presentation. Front. Immunol. 2021 12 636568 10.3389/fimmu.2021.636568 33767702
    [Google Scholar]
  40. Zhang A. Fan T. Liu Y. Yu G. Li C. Jiang Z. Regulatory T cells in immune checkpoint blockade antitumor therapy. Mol. Cancer 2024 23 1 251 10.1186/s12943‑024‑02156‑y 39516941
    [Google Scholar]
  41. Tu Z. Li K. Ji Q. Huang Y. Lv S. Li J. Wu L. Huang K. Zhu X. Pan-cancer analysis: Predictive role of TAP1 in cancer prognosis and response to immunotherapy. BMC Cancer 2023 23 1 133 10.1186/s12885‑022‑10491‑w 36759763
    [Google Scholar]
  42. Romero J.M. Jiménez P. Cabrera T. Cózar J.M. Pedrinaci S. Tallada M. Garrido F. Ruiz-Cabello F. Coordinated downregulation of the antigen presentation machinery and HLA class I/β2-microglobulin complex is responsible for HLA-ABC loss in bladder cancer. Int. J. Cancer 2005 113 4 605 610 10.1002/ijc.20499 15455355
    [Google Scholar]
  43. Lou Y. Vitalis T.Z. Basha G. Cai B. Chen S.S. Choi K.B. Jeffries A.P. Elliott W.M. Atkins D. Seliger B. Jefferies W.A. Restoration of the expression of transporters associated with antigen processing in lung carcinoma increases tumor-specific immune responses and survival. Cancer Res. 2005 65 17 7926 7933 10.1158/0008‑5472.CAN‑04‑3977 16140964
    [Google Scholar]
  44. Oronsky B. Abrouk N. Caroen S. Lybeck M. Guo X. Wang X. Yu Z. Reid T. A 2022 update on extensive stage small-cell lung cancer (SCLC). J. Cancer 2022 13 9 2945 2953 10.7150/jca.75622 35912017
    [Google Scholar]
  45. Yang W. Li Y. Gao R. Xiu Z. Sun T. MHC class I dysfunction of glioma stem cells escapes from CTL-mediated immune response via activation of Wnt/β-catenin signaling pathway. Oncogene 2020 39 5 1098 1111 10.1038/s41388‑019‑1045‑6 31591480
    [Google Scholar]
  46. Ylitalo E.B. Thysell E. Jernberg E. Lundholm M. Crnalic S. Egevad L. Stattin P. Widmark A. Bergh A. Wikström P. Subgroups of castration-resistant prostate cancer bone metastases defined through an inverse relationship between androgen receptor activity and immune response. Eur. Urol. 2017 71 5 776 787 10.1016/j.eururo.2016.07.033 27497761
    [Google Scholar]
  47. Bandoh N. Ogino T. Katayama A. Takahara M. Katada A. Hayashi T. Harabuchi Y. HLA class I antigen and transporter associated with antigen processing downregulation in metastatic lesions of head and neck squamous cell carcinoma as a marker of poor prognosis. Oncol. Rep. 2010 23 4 933 939 10.3892/or_00000717 20204276
    [Google Scholar]
  48. Zhu R. Chen Y.T. Wang B.W. You Y.Y. Wang X.H. Xie H.T. Jiang F.G. Zhang M.C. TAP1, a potential immune-related prognosis biomarker with functional significance in uveal melanoma. BMC Cancer 2023 23 1 146 10.1186/s12885‑023‑10527‑9 36774490
    [Google Scholar]
  49. Bubeník J. MHC class I down-regulation: Tumour escape from immune surveillance? (Review). Int. J. Oncol. 2004 25 2 487 491 10.3892/ijo.25.2.487 15254748
    [Google Scholar]
  50. Garrido G. Schrand B. Rabasa A. Levay A. D’Eramo F. Berezhnoy A. Modi S. Gefen T. Marijt K. Doorduijn E. Dudeja V. van Hall T. Gilboa E. Tumor-targeted silencing of the peptide transporter TAP induces potent antitumor immunity. Nat. Commun. 2019 10 1 3773 10.1038/s41467‑019‑11728‑2 31434881
    [Google Scholar]
  51. Ritter C. Fan K. Paschen A. Reker Hardrup S. Ferrone S. Nghiem P. Ugurel S. Schrama D. Becker J.C. Epigenetic priming restores the HLA class-I antigen processing machinery expression in Merkel cell carcinoma. Sci. Rep. 2017 7 1 2290 10.1038/s41598‑017‑02608‑0 28536458
    [Google Scholar]
  52. Khalaf K. Hana D. Chou J.T.T. Singh C. Mackiewicz A. Kaczmarek M. Aspects of the tumor microenvironment involved in immune resistance and drug resistance. Front. Immunol. 2021 12 656364 10.3389/fimmu.2021.656364 34122412
    [Google Scholar]
  53. Worthington J.J. Fenton T.M. Czajkowska B.I. Klementowicz J.E. Travis M.A. Regulation of TGFβ in the immune system: An emerging role for integrins and dendritic cells. Immunobiology 2012 217 12 1259 1265 10.1016/j.imbio.2012.06.009 22902140
    [Google Scholar]
  54. Blades R.A. Keating P.J. McWilliam L.J. George N.J.R. Stern P.L. Loss of HLA class I expression in prostate cancer: Implications for immunotherapy. Urology 1995 46 5 681 687 10.1016/S0090‑4295(99)80301‑X 7495121
    [Google Scholar]
  55. Fu L. Zhang C. Wang Z. Tao W. Zhu J. Zhou Y. Sun C. Xue B. Yu M. Xu L. Zang Y. Clinical application of serum tumor abnormal protein in prostate cancer patients. BMC Cancer 2024 24 1 665 10.1186/s12885‑024‑12418‑z 38822321
    [Google Scholar]
  56. dos Reis F.D. Jerónimo C. Correia M.P. Epigenetic modulation and prostate cancer: Paving the way for NK cell anti-tumor immunity. Front. Immunol. 2023 14 1152572 10.3389/fimmu.2023.1152572 37090711
    [Google Scholar]
  57. Restifo N.P. Esquivel F. Kawakami Y. Yewdell J.W. Mulé J.J. Rosenberg S.A. Bennink J.R. Identification of human cancers deficient in antigen processing. J. Exp. Med. 1993 177 2 265 272 10.1084/jem.177.2.265 8426105
    [Google Scholar]
  58. Feliu N. Hassan M. Garcia Rico E. Cui D. Parak W. Alvarez-Puebla R. SERS quantification and characterization of proteins and other biomolecules. Langmuir 2017 33 38 9711 9730 10.1021/acs.langmuir.7b01567 28826207
    [Google Scholar]
  59. Hanahan D. Hallmarks of cancer: New dimensions. Cancer Discov. 2022 12 1 31 46 10.1158/2159‑8290.CD‑21‑1059 35022204
    [Google Scholar]
  60. Dwivedi S. Goel A. Khattri S. Sharma P. Pant K.K. Aggravation of inflammation by smokeless tobacco in comparison of smoked tobacco. Indian J. Clin. Biochem. 2015 30 1 117 119 10.1007/s12291‑014‑0467‑8 25646053
    [Google Scholar]
  61. Dwivedi S. Goel A. Khattri S. Mandhani A. Sharma P. Pant K.K. Tobacco exposure by various modes may alter proinflammatory (IL-12) and anti-inflammatory (IL-10) levels and affects the survival of prostate carcinoma patients: An explorative study in North Indian population. BioMed Res. Int. 2014 2014 1 1 11 10.1155/2014/158530 25177683
    [Google Scholar]
  62. Pant K.K. Dwivedi S. Goel A. Mandhani A. Khattri S. Tobacco exposure may enhance inflammation in prostate carcinoma patients: An explorative study in north Indian population. Toxicol. Int. 2012 19 3 310 318 10.4103/0971‑6580.103681 23293472
    [Google Scholar]
  63. Ngadikun Pradjatmo H. Nugroho K.A. Pasala M. Prasetyastuti Analysis of erythrocyte sedimentation rate order in epithelial ovarian cancer. J. Cancer 2023 14 12 2173 2180 10.7150/jca.82941 37576394
    [Google Scholar]
  64. Shetty A.A. Gupta N. Saigal S. Bhargava A. Giri D. Mondal A. Dagli N. Mehta D. Comprehensive assessment of albumin and uric acid levels in oral submucous fibrosis: A comparative case-control study involving different risk groups. Cureus 2023 15 12 e49811 10.7759/cureus.49811 38169924
    [Google Scholar]
  65. Sandilands E.A. Dhaun N. Dear J.W. Webb D.J. Measurement of renal function in patients with chronic kidney disease. Br. J. Clin. Pharmacol. 2013 76 4 504 515 10.1111/bcp.12198 23802624
    [Google Scholar]
  66. Moreira A.C. Mesquita G. Gomes M.S. Ferritin: An inflammatory player keeping iron at the core of pathogen-host interactions. Microorganisms 2020 8 4 589 10.3390/microorganisms8040589 32325688
    [Google Scholar]
  67. Mahroum N. Alghory A. Kiyak Z. Alwani A. Seida R. Alrais M. Shoenfeld Y. Ferritin – from iron, through inflammation and autoimmunity, to COVID-19. J. Autoimmun. 2022 126 102778 10.1016/j.jaut.2021.102778 34883281
    [Google Scholar]
  68. Rizo-Téllez S.A. Sekheri M. Filep J.G. C-reactive protein: A target for therapy to reduce inflammation. Front. Immunol. 2023 14 1237729 10.3389/fimmu.2023.1237729 37564640
    [Google Scholar]
  69. Salema H. Joshi S. Pawar S. Nair V.S. Deo V.V. Sanghai M.M. Evaluation of the role of C-reactive protein as a prognostic indicator in oral pre-malignant and malignant lesions. Cureus 2024 16 5 e60812 10.7759/cureus.60812 38910781
    [Google Scholar]
  70. Wen Y. Zhu Y. Zhang C. Yang X. Gao Y. Li M. Yang H. Liu T. Tang H. Chronic inflammation, cancer development and immunotherapy. Front. Pharmacol. 2022 13 1040163 10.3389/fphar.2022.1040163 36313280
    [Google Scholar]
  71. Afify S.M. Hassan G. Seno A. Seno M. Cancer-inducing niche: The force of chronic inflammation. Br. J. Cancer 2022 127 2 193 201 10.1038/s41416‑022‑01775‑w 35292758
    [Google Scholar]
  72. Tan Y. Wang Z. Xu M. Li B. Huang Z. Qin S. Nice E.C. Tang J. Huang C. Oral squamous cell carcinomas: State of the field and emerging directions. Int. J. Oral Sci. 2023 15 1 44 10.1038/s41368‑023‑00249‑w 37736748
    [Google Scholar]
  73. Barbet G. Nair-Gupta P. Schotsaert M. Yeung S.T. Moretti J. Seyffer F. Metreveli G. Gardner T. Choi A. Tortorella D. Tampé R. Khanna K.M. García-Sastre A. Blander J.M. TAP dysfunction in dendritic cells enables noncanonical cross-presentation for T cell priming. Nat. Immunol. 2021 22 4 497 509 10.1038/s41590‑021‑00903‑7 33790474
    [Google Scholar]
  74. Pishesha N. Harmand T.J. Ploegh H.L. A guide to antigen processing and presentation. Nat. Rev. Immunol. 2022 22 12 751 764 10.1038/s41577‑022‑00707‑2 35418563
    [Google Scholar]
  75. Basler M. Kirk C.J. Groettrup M. The immunoproteasome in antigen processing and other immunological functions. Curr. Opin. Immunol. 2013 25 1 74 80 10.1016/j.coi.2012.11.004 23219269
    [Google Scholar]
  76. Doty D.T. Schueler J. Mott V.L. Bryan C.M. Moore N.F. Ho J.C. Borenstein J.T. Modeling immune checkpoint inhibitor efficacy in syngeneic mouse tumors in an ex vivo immuno-oncology dynamic environment. Int. J. Mol. Sci. 2020 21 18 6478 10.3390/ijms21186478 32899865
    [Google Scholar]
/content/journals/emiddt/10.2174/0118715303344715241225184322
Loading
/content/journals/emiddt/10.2174/0118715303344715241225184322
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher's website along with the published article.

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test