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Volume 2, Issue 1, Pp 14-18, 2024

DOI: 10.61784/wjbs240143


Blunk Dennis


Department of Pharmaceutical Technology, University of Regensburg, Regensburg, Germany.

Corresponding Author

Blunk Dennis


In the past decade, colorectal cancer immunotherapy has made great progress, especially for mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer phenotypes, immunotherapy has sustained therapeutic responses, and achieved significant clinical efficacy. However, most metastatic colorectal cancers are non-mismatch repair deficient (pMMR) or microsatellite stable (MSS), and these patients benefit less from immune checkpoint inhibitors (ICIs). With the widespread development of clinical trials of ICIs in colorectal cancer, immunotherapy has gradually expanded its indications due to its proven efficacy, and has become the standard first-line treatment for patients with dMMR/MSI-H advanced colorectal cancer. For patients with pMMR/MSS, ICIs have also shown potential therapeutic effects by combining chemotherapy and targeted therapy. This article mainly discusses the application of ICIs in colorectal cancer, analyzes the relationship between tumors and the immune system, and outlines the immunological characteristics and classification of colorectal cancer as well as the latest progress of ICIs in the treatment of colorectal cancer.


Colorectal tumors; Immune checkpoint inhibitors; Immunity therapy; Biomarkers


Blunk Dennis. The relationship between immune checkpoint inhibitors in colorectal cancer. World Journal of Biomedical Sciences. 2024, 2(1): 14-18. DOI: 10.61784/wjbs240143.


[1] Bray F, Ferlay J, Soerjomataram I. 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.

[2] Le DT, Kim TW, Van Cutsem E. Phase Ⅱ Open-Label Study of Pembrolizumab in treatment-refractory, microsatellite instability-high/ mismatch repair-deficient metastatic colorectal cancer: KEYNOTE- 164 . J Clin Oncol, 2020, 38( 1): 11- 19.

[3] FDA. FDA approves first cancer treatment for any solid tumor with a specific genetic feature. 2017-05-23. https://www. fda. gov/ news-events/press-announcements/fda-approves-first-cancer-reatment- any-solid-tumor-specific-genetic-feature.

[4] Overman MJ, McDermott R, Leach JL. 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.

[5] FDA. FDA grants accelerated approval to ipilimumab for MSI-H or dMMR metastatic colorectal cancer. 2018-7- 11. https://www. fdagov/drugs/resources-information-approved-drugs/fda-grants-accelerated- approval-ipilimumab-msi-h-or-dmmr-metastatic-colorectal-cancer.

[6] FDA. FDA grants nivolumab accelerated approval for MSI-H or dMMR colorectal cancer. 2017-08-01. https://www. fda. gov/ drugs/resources-information-approved-drugs/fda-grants-nivolumab- accelerated-approval-msi-h-or-dmmr-colorectal-cancer.

[7] Andre T, Shiu KK, Kim TW. Pembrolizumab in microsatellite- instability-high advanced colorectal cancer . N Engl J Med, 2020,383(23): 2207-2218.

[8] FDA. FDA approves pembrolizumab for first-line treatment of MSI-H/ dMMR colorectal cancer. 2020-6-30. https://www. fda. gov/ drugs/drug-approvals-and-databases/fda-approves-pembrolizumab- first-line-treatment-msi-hdmmr-colorectal-cancer.

[9] Andre T, Shiu K-K, Kim TW. Final overall survival for the phase Ⅲ KN177 study: Pembrolizumab versus chemotherapy in microsatellite instability-high/mismatch repair deficient (MSI-H/ dMMR) metastatic colorectal cancer (mCRC) .J Clin Oncol, 2021, 39( 15_suppl): 3500.

[10] 1Brunner MC, Chambers CA, Chan FK. CTLA-4-Mediated inhibition of early events of T cell proliferation . J Immunol, 1999, 162( 10): 5813-5820.

[11] Linsley PS, Greene JL, Brady W. Human B7- 1 (CD80) and B7-2 (CD86) bind with similar avidities but distinct kinetics to CD28 and CTLA-4 receptors . Immunity, 1994, 1(9): 793-801.

[12] Bachmann MF, K?hler G, Ecabert B. Cutting edge: lymphoproliferative disease in the absence of CTLA-4 is not T cell autonomous . J Immunol, 1999, 163(3): 1128- 1131.

[13] Matheu MP, Othy S, Greenberg ML. Imaging regulatory T cell dynamics and CTLA4-mediated suppression of T cell priming . Nat Commun, 2015, 6: 6219.

[14] Jain N, Nguyen H, Chambers C. Dual function of CTLA-4 in regulatory T cells and conventional T cells to prevent multiorgan autoimmunity . Proc Natl Acad Sci U SA, 2010, 107(4): 1524- 1528.

[15] Herbst RS, Soria JC, Kowanetz M. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients . Nature, 2014, 515(7528): 563-567.

[16] Yarchoan M, Hopkins A, Jaffee EM. Tumor mutational burden and response rate to PD- 1 inhibition . N Engl J Med, 2017, 377(25): 2500-2501.

[17] Guinney J, Dienstmann R, Wang X. The consensus molecular subtypes of colorectal cancer . Nat Med, 2015, 21( 11): 1350- 1356.

[18] Ganesh K, Stadler ZK, Cercek A. Immunotherapy in colorectal cancer: rationale, challenges and potential . Nat Rev Gastroenterol Hepatol, 2019, 16(6): 361-375.

[19] Samstein RM, Lee CH, Shoushtari AN. Tumor mutational load predicts survival after immunotherapy across multiple cancer types . Nat Genet, 2019, 51(2): 202-206.

[20] Chan TA, Yarchoan M, Jaffee E. Development of tumor mutation burden as an immunotherapy biomarker: utility for the oncology clinic . Ann Oncol, 2019, 30( 1): 44-56.

[21] Le DT, Durham JN, Smith KN. Mismatch repair deficiency predicts response of solid tumors to PD- 1 blockade . Science, 2017, 357(6349): 409-413.

[22] 2Roth MT, Das S. Pembrolizumab in unresectable or metastatic MSI- high colorectal cancer: safety and efficacy . Expert Rev Anticancer Ther, 2021, 21(2): 229-238.

[23] Wang QX, Qu CH, Gao YH. The degree of microsatellite instability predicts response to PD- 1 blockade immunotherapy in mismatch repair-deficient/microsatellite instability-high colorectal cancers . Exp Hematol Oncol, 2021, 10( 1): 2.

[24] Chalabi M, Fanchi LF, Dijkstra KK. Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers . Nat Med, 2020, 26(4): 566-576.

[25] Yuki S, Bando H, Tsukada Y. Short-term results of VOLTAGE- A: Nivolumab monotherapy and subsequent radical surgery following spanoperative chemoradiotherapy inpatients with microsatellite stable and microsatellite instability-high locally advanced rectal cancer . J Clin Oncol 2020, 38( 15_suppl): 4100.

[26] Chen EX, Jonker DJ, Loree JM. Effect of combined immune checkpoint inhibition vs best supportive care alone in patients with advanced colorectal cancer: The Canadian Cancer Trials Group CO.26 Study .JAMA Oncol,2020, 6(6): 831-838.

[27] Wang L, Hui H, Agrawal K. m(6) A RNA methyltransferases METTL3/ 14 regulate immune responses to anti-PD- 1 therapy . Embo J, 2020, 39(20): e104514.

[28] Segal NH, Cercek A, Ku G. Phase II single-arm study of Durvalumab and Tremelimumab with concurrent radiotherapy in patients with mismatch repair-proficient metastatic colorectal cancer . Clin Cancer Res, 2021, 27(8): 2200-2208.

[29] MonjazebAM, Giobbie-HurderA, LakoA. A randomized trial of combined PD-L1 and CTLA-4 inhibition with targeted low-dose or hypofractionated radiation for patients with metastatic colorectal cancer . Clin Cancer Res, 2021, 27(9): 2470-2480.

[30] Marabelle A, Fakih M, Lopez J. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with Pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE- 158 study . Lancet Oncol, 2020, 21( 10): 1353- 1365.

[31] Bergqvist V, Hertervig E, Gedeon P. Vedolizumab treatment for immune checkpoint inhibitor-induced enterocolitis . Cancer Immunol Immunother, 2017, 66(5): 581-592.

[32] Brahmer JR, Lacchetti C, Schneider BJ. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology Clinical Practice Guideline . J Clin Oncol, 2018, 36( 17): 1714- 1768.

[33] Lee JH, Long GV, Menzies AM. Association between circulating tumor DNA and pseudoprogression in patients with metastatic melanoma treated with anti-programmed cell death 1 antibodies . JAMA Oncol, 2018, 4(5): 717-721.

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