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Advances in immune therapies for the treatment of microsatellite instability‑high/deficient mismatch repair metastatic colorectal cancer (Review)

  • Authors:
    • Khalil Choucair
    • Maluki Radford
    • Ajay Bansal
    • Robin Park
    • Anwaar Saeed
  • View Affiliations / Copyright

    Affiliations: Department of Medicine, Kansas University School of Medicine, Wichita, KS 67214, USA, Department of Medicine, Kansas University Medical Center, Kansas City, KS 66205, USA, Department of Medicine, Division of Gastroenterology and Hepatology, University of Kansas Medical Center and Kansas Cancer Institute, Kansas City, KS 66205, USA, Department of Medicine, MetroWest Medical Center/Tufts University School of Medicine, Framingham, Massachusetts, MA 01702, USA, Department of Medicine, Division of Medical Oncology, Kansas University Cancer Center, Kansas City, KS 66205, USA
    Copyright: © Choucair et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 74
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    Published online on: August 11, 2021
       https://doi.org/10.3892/ijo.2021.5254
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Abstract

Microsatellite instability‑high/deficient mismatch repair colorectal cancer (MSI‑H/dMMR CRC) is a molecular subtype characterized by high‑frequency mutations within DNA mismatch repair genes. Defects in the DNA mismatch repair machinery lead to subsequent frame‑shift mutations, resulting in the generation of frame‑shift peptides that serve as neoantigens. This has translated into exquisite sensitivity to immune checkpoint inhibitors (ICIs) and a significant clinical benefit from immune therapies in this patient population. The present article provides a comprehensive review of the advances in the field of immune therapies for MSI‑H/dMMR metastatic CRC, with a focus on the major randomized clinical trials that led to Food and Drug Administration approval of specific ICIs for this population, a detailed review of the molecular background responsible for tumor response, as well as the mechanisms of resistance to ICI therapy. Finally, ongoing investigations of other immunotherapeutic strategies to address and overcome the challenges that currently limit response and long‑term response to ICIs were presented.
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1 

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71:209–249. 2021. View Article : Google Scholar

2 

Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC, Cercek A, Smith RA and Jemal A: Colorectal cancer statistics, 2020. CA Cancer J Clin. 70:145–164. 2020. View Article : Google Scholar

3 

Pearlman R, Frankel WL, Swanson B, Zhao W, Yilmaz A, Miller K, Bacher J, Bigley C, Nelsen L, Goodfellow PJ, et al: Prevalence and spectrum of germline cancer susceptibility gene mutations among patients with early-onset colorectal cancer. JAMA Oncol. 3:464–471. 2017. View Article : Google Scholar

4 

Hull R, Francies FZ, Oyomno M and Dlamini Z: Colorectal cancer genetics, incidence and risk factors: In search for targeted therapies. Cancer Manag Res. 12:9869–9882. 2020. View Article : Google Scholar

5 

Koopman M, Kortman GAM, Mekenkamp L, Ligtenberg MJ, Hoogerbrugge N, Antonini NF, Punt CJ and van Krieken JH: Deficient mismatch repair system in patients with sporadic advanced colorectal cancer. Br J Cancer. 100:266–273. 2009. View Article : Google Scholar

6 

Venderbosch S, Nagtegaal ID, Maughan TS, Smith CG, Cheadle JP, Fisher D, Kaplan R, Quirke P, Seymour MT, Richman SD, et al: Mismatch repair status and BRAF mutation status in metastatic colorectal cancer patients: A pooled analysis of the CAIRO, CAIRO2, COIN, and FOCUS studies. Clin Cancer Res. 20:5322–5330. 2014. View Article : Google Scholar

7 

Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, et al: PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 372:2509–2520. 2015. View Article : Google Scholar

8 

Morse MA, Hochster H and Benson A: Perspectives on treatment of metastatic colorectal cancer with immune checkpoint inhibitor therapy. Oncologist. 25:33–45. 2020. View Article : Google Scholar

9 

Chau I and Cunningham D: Treatment in advanced colorectal cancer: What, when and how? Br J Cancer. 100:1704–1719. 2009. View Article : Google Scholar

10 

Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, Lu S, Kemberling H, Wilt C, Luber BS, et al: Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 357:409–413. 2017. View Article : Google Scholar

11 

Overman MJ, McDermott R, Leach JL, Lonardi S, Lenz HJ, Morse MA, Desai J, Hill A, Axelson M, Moss RA, et al: 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. 18:1182–1191. 2017. View Article : Google Scholar

12 

Pardoll DM: The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 12:252–264. 2012. View Article : Google Scholar

13 

Saunders PA, Hendrycks VR, Lidinsky WA and Woods ML: PD-L2:PD-1 involvement in T cell proliferation, cytokine production, and integrin-mediated adhesion. Eur J Immunol. 35:3561–3569. 2005. View Article : Google Scholar

14 

Sharma P and Allison JP: Immune checkpoint targeting in cancer therapy: Toward combination strategies with curative potential. Cell. 161:205–214. 2015. View Article : Google Scholar

15 

Ijsselsteijn ME, Petitprez F, Lacroix L, Ruano D, van der Breggen R, Julie C, Morreau H, Sautès-Fridman C, Fridman WH and de Miranda NFDCC: Revisiting immune escape in colorectal cancer in the era of immunotherapy. Br J Cancer. 120:815–818. 2019. View Article : Google Scholar

16 

Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, et al: Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 363:711–723. 2010. View Article : Google Scholar

17 

Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, Hassel JC, Rutkowski P, McNeil C, Kalinka-Warzocha E, et al: Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 372:320–330. 2015. View Article : Google Scholar

18 

Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, Patnaik A, Aggarwal C, Gubens M, Horn L, et al: Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 372:2018–2028. 2015. View Article : Google Scholar

19 

Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, et al: Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 373:123–135. 2015. View Article : Google Scholar

20 

Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, et al: Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 373:1627–1639. 2015. View Article : Google Scholar

21 

Schadendorf D, Hodi FS, Robert C, Weber JS, Margolin K, Hamid O, Patt D, Chen TT, Berman DM and Wolchok JD: Pooled analysis of long-term survival data from phase II and phase III trials of ipilimumab in unresectable or metastatic melanoma. J Clin Oncol. 33:1889–1894. 2015. View Article : Google Scholar

22 

Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, Lee W, Yuan J, Wong P, Ho TS, et al: Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 348:124–128. 2015. View Article : Google Scholar

23 

Schumacher TN and Schreiber RD: Neoantigens in cancer immunotherapy. Science. 348:69–74. 2015. View Article : Google Scholar

24 

Subbiah V, Solit DB, Chan TA and Kurzrock R: The FDA approval of pembrolizumab for adult and pediatric patients with tumor mutational burden (TMB) ≥10: A decision centered on empowering patients and their physicians. Ann Oncol. 31:1115–1118. 2020. View Article : Google Scholar

25 

Mlecnik B, Tosolini M, Kirilovsky A, Berger A, Bindea G, Meatchi T, Bruneval P, Trajanoski Z, Fridman WH, Pagès F and Galon J: Histopathologic-based prognostic factors of colorectal cancers are associated with the state of the local immune reaction. J Clin Oncol. 29:610–618. 2011. View Article : Google Scholar

26 

Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pagès C, Tosolini M, Camus M, Berger A, Wind P, et al: Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 313:1960–1964. 2006. View Article : Google Scholar

27 

Galon J, Fridman WH and Pagès F: The adaptive immunologic microenvironment in colorectal cancer: A novel perspective. Cancer Res. 67:1883–1886. 2007. View Article : Google Scholar

28 

Franke AJ, Skelton WP, Starr JS, Parekh H, Lee JJ, Overman MJ, Allegra C and George TJ: Immunotherapy for colorectal cancer: A review of current and novel therapeutic approaches. J Natl Cancer Inst. 111:1131–1141. 2019. View Article : Google Scholar

29 

Shia J, Holck S, DePetris G, Greenson JK and Klimstra DS: Lynch syndrome-associated neoplasms: A discussion on histopathology and immunohistochemistry. Fam Cancer. 12:241–260. 2013. View Article : Google Scholar

30 

Choi YY, Bae JM, An JY, Kwon IG, Cho I, Shin HB, Eiji T, Aburahmah M, Kim HI, Cheong JH, et al: Is microsatellite instability a prognostic marker in gastric cancer? A systematic review with meta-analysis. J Surg Oncol. 110:129–135. 2014. View Article : Google Scholar

31 

Llosa NJ, Cruise M, Tam A, Wicks EC, Hechenbleikner EM, Taube JM, Blosser RL, Fan H, Wang H, Luber BS, et al: The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints. Cancer Discov. 5:43–51. 2015. View Article : Google Scholar

32 

Lagos GG, Izar B and Rizvi NA: Beyond tumor PD-L1: Emerging genomic biomarkers for checkpoint inhibitor immunotherapy. Am Soc Clin Oncol Educ Book. 40:1–11. 2020.

33 

Choucair K, Morand S, Stanbery L, Edelman G, Dworkin L and Nemunaitis J: TMB: A promising immune-response biomarker, and potential spearhead in advancing targeted therapy trials. Cancer Gene Ther. 27:841–853. 2020. View Article : Google Scholar

34 

Bever KM and Le DT: An expanding role for immunotherapy in colorectal cancer. J Natl Compr Canc Netw. 15:401–410. 2017. View Article : Google Scholar

35 

Vignali DA and Kuchroo VK: IL-12 family cytokines: Immunological playmakers. Nat Immunol. 13:722–728. 2012. View Article : Google Scholar

36 

Kim TM, Laird PW and Park PJ: The landscape of microsatellite instability in colorectal and endometrial cancer genomes. Cell. 155:858–868. 2013. View Article : Google Scholar

37 

Price TJ, Thavaneswaran S, Burge M, Segelov E, Haller DG, Punt CJ, Arnold D, Karapetis CS, Tebbutt NC, Pavlakis N, et al: Update on optimal treatment for metastatic colorectal cancer from the ACTG/AGITG expert meeting: ECCO. 2015.Expert Rev Anticancer Ther. 16:557–571. 2016. View Article : Google Scholar

38 

Valero C, Lee M, Hoen D, Zehir A, Berger MF, Seshan VE, Chan TA and Morris LGT: Response rates to anti-PD-1 immunotherapy in microsatellite-stable solid tumors with 10 or more mutations per megabase. JAMA Oncol. 7:739–743. 2021. View Article : Google Scholar

39 

Segal NH, Parsons DW, Peggs KS, Velculescu V, Kinzler KW, Vogelstein B and Allison JP: Epitope landscape in breast and colorectal cancer. Cancer Res. 68:889–892. 2008. View Article : Google Scholar

40 

Kloor M and von Knebel Doeberitz M: The immune biology of microsatellite-unstable cancer. Trends Cancer. 2:121–133. 2016. View Article : Google Scholar

41 

Bauer K, Nelius N, Reuschenbach M, Koch M, Weitz J, Steinert G, Kopitz J, Beckhove P, Tariverdian M, von Knebel Doeberitz M and Kloor M: T cell responses against microsatellite instability-induced frameshift peptides and influence of regulatory T cells in colorectal cancer. Cancer Immunol Immunother. 62:27–37. 2013. View Article : Google Scholar

42 

Kloor M, Reuschenbach M, Pauligk C, Karbach J, Rafiyan MR, Al-Batran SE, Tariverdian M, Jäger E and von Knebel Doeberitz M: A frameshift peptide neoantigen-based vaccine for mismatch repair-deficient cancers: A phase I/IIa clinical trial. Clin Cancer Res. 26:4503–4510. 2020. View Article : Google Scholar

43 

Reuschenbach M, Kloor M, Morak M, Wentzensen N, Germann A, Garbe Y, Tariverdian M, Findeisen P, Neumaier M, Holinski-Feder E and von Knebel Doeberitz M: Serum antibodies against frameshift peptides in microsatellite unstable colorectal cancer patients with Lynch syndrome. Fam Cancer. 9:173–179. 2010. View Article : Google Scholar

44 

Ballhausen A, Przybilla MJ, Jendrusch M, Haupt S, Pfaffendorf E, Draxlbauer M, Seidler F, Krausert S, Ahadova A, Kalteis MS, et al: The shared neoantigen landscape of MSI cancers reflects immunoediting during tumor evolution. bioRxiv. Jan 1–2019.Epub ahead of print.

45 

Rus Bakarurraini NAA, Ab Mutalib NS and Jamal R: Abu N. The landscape of tumor-specific antigens in colorectal cancer. Vaccines (Basel). 8:3712020. View Article : Google Scholar

46 

Yang G, Zheng R and Jin Z: Correlations between microsatellite instability and the biological behaviour of tumours. J Cancer Res Clin Oncol. 145:2891–2899. 2019. View Article : Google Scholar

47 

Kim NG, Rhee H, Li LS and Kim H, Lee JS, Kim JH, Kim NK and Kim H: Identification of MARCKS, FLJ11383 and TAF1B as putative novel target genes in colorectal carcinomas with microsatellite instability. Oncogene. 21:5081–5087. 2002. View Article : Google Scholar

48 

Itatani Y, Kawada K and Sakai Y: Transforming growth factor-β signaling pathway in colorectal cancer and its tumor microenvironment. Int J Mol Sci. 20:58222019. View Article : Google Scholar

49 

Bickeböller M, Tagscherer KE, Kloor M, Jansen L, Chang-Claude J, Brenner H, Hoffmeister M, Toth C, Schirmacher P, Roth W and Bläker H: Functional characterization of the tumor-suppressor MARCKS in colorectal cancer and its association with survival. Oncogene. 34:1150–1159. 2015. View Article : Google Scholar

50 

Hornung V, Ablasser A, Charrel-Dennis M, Bauernfeind F, Horvath G, Caffrey DR, Latz E and Fitzgerald KA: AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature. 458:514–518. 2009. View Article : Google Scholar

51 

Xu M, Wang J, Li H, Zhang Z and Cheng Z: AIM2 inhibits colorectal cancer cell proliferation and migration through suppression of Gli1. Aging (Albany NY). 13:1017–1031. 2020. View Article : Google Scholar

52 

Ivanov I, Lo KC, Hawthorn L, Cowell JK and Ionov Y: Identifying candidate colon cancer tumor suppressor genes using inhibition of nonsense-mediated mRNA decay in colon cancer cells. Oncogene. 26:2873–2884. 2007. View Article : Google Scholar

53 

Tougeron D, Fauquembergue E, Rouquette A, Le Pessot F, Sesboüé R, Laurent M, Berthet P, Mauillon J, Di Fiore F, Sabourin JC, et al: Tumor-infiltrating lymphocytes in colorectal cancers with microsatellite instability are correlated with the number and spectrum of frameshift mutations. Mod Pathol. 22:1186–1195. 2009. View Article : Google Scholar

54 

Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, et al: Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 366:2443–2454. 2012. View Article : Google Scholar

55 

Brahmer JR, Drake CG, Wollner I, Powderly JD, Picus J, Sharfman WH, Stankevich E, Pons A, Salay TM, McMiller TL, et al: Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: Safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol. 28:3167–3175. 2010. View Article : Google Scholar

56 

Giardiello FM, Allen JI, Axilbund JE, Boland CR, Burke CA, Burt RW, Church JM, Dominitz JA, Johnson DA, Kaltenbach T, et al: Guidelines on genetic evaluation and management of Lynch syndrome: A consensus statement by the US multi-society task force on colorectal cancer. Gastroenterology. 147:502–526. 2014. View Article : Google Scholar

57 

Stoffel EM, Mangu PB, Gruber SB, Hamilton SR, Kalady MF, Lau MW, Lu KH, Roach N and Limburg PJ; American Society of Clinical Oncology; European Society of Clinical Oncology: Hereditary colorectal cancer syndromes: American society of clinical oncology clinical practice guideline endorsement of the familial risk-colorectal cancer: European society for medical oncology clinical practice guidelines. J Clin Oncol. 33:209–217. 2015. View Article : Google Scholar

58 

Luchini C, Bibeau F, Ligtenberg MJL, Singh N, Nottegar A, Bosse T, Miller R, Riaz N, Douillard JY, Andre F and Scarpa A: ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: A systematic review-based approach. Ann Oncol. 30:1232–1243. 2019. View Article : Google Scholar

59 

Monahan KJ, Bradshaw N, Dolwani S, Desouza B, Dunlop MG, East JE, Ilyas M, Kaur A, Lalloo F, Latchford A, et al: Guidelines for the management of hereditary colorectal cancer from the British society of gastroenterology (BSG)/association of coloproctology of Great Britain and Ireland (ACPGBI)/United Kingdom cancer genetics group (UKCGG). Gut. 69:411–444. 2020. View Article : Google Scholar

60 

Stein A, Moehler M, Trojan J, Goekkurt E and Vogel A: Immuno-oncology in GI tumours: Clinical evidence and emerging trials of PD-1/PD-L1 antagonists. Crit Rev Oncol Hematol. 130:13–26. 2018. View Article : Google Scholar

61 

FDA approves pembrolizumab for first-line treatment of MSI-H/dMMR colorectal cancer. FDA; 2020

62 

Le DT, Kim TW, Van Cutsem E, Geva R, Jäger D, Hara H, Burge M, O'Neil B, Kavan P, Yoshino T, et al: Phase II open-label study of pembrolizumab in treatment-refractory, microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: KEYNOTE-164. J Clin Oncol. 38:11–19. 2020. View Article : Google Scholar

63 

US. Food and drug administration: KEYTRUDA (pembrolizumab) {package insert}. 2017.

64 

Andre T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt CJA, Smith DM, Garcia-Carbonero R, Benavides M, Gibbs P, et al: Pembrolizumab versus chemotherapy for microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer: The phase 3 KEYNOTE-177 study. J Clin Oncol. 38(18 Suppl): LBA42020. View Article : Google Scholar

65 

Shiu KK, Andre T, Kim TW, Jensen BV, Jensen LH, Punt cJA, Smith DM, Garcia-Carbonero R, Benavides M, Gibbs P, et al: KEYNOTE-177: Phase III randomized study of pembrolizumab versus chemotherapy for microsatellite instability-high advanced colorectal cancer. J Clin Oncol. 39(3 Suppl): S62021. View Article : Google Scholar

66 

FDA grants nivolumab accelerated approval for MSI-H or dMMR colorectal cancer. FDA; 2017

67 

Das R, Verma R, Sznol M, Boddupalli CS, Gettinger SN, Kluger H, Callahan M, Wolchok JD, Halaban R, Dhodapkar MV and Dhodapkar KM: Combination therapy with anti-CTLA-4 and anti-PD-1 leads to distinct immunologic changes in vivo. J Immunol. 194:950–959. 2015. View Article : Google Scholar

68 

Lenz HJJ, Van Cutsem E, Limon ML, Wong KY, Hendlisz A, Aglietta M, Garcia-Alfonso P, Neyns B, Luppi G, Cardin D, et al: Durable clinical benefit with nivolumab (NIVO) plus low-dose ipilimumab (IPI) as first-line therapy in microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC). Ann Oncol. 29(Suppl 8): viii7142018. View Article : Google Scholar

69 

FDA grants accelerated approval to ipilimumab for MSI-H or dMMR metastatic colorectal cancer. FDA; 2018

70 

Chung KY, Gore I, Fong L, Venook A, Beck SB, Dorazio P, Criscitiello PJ, Healey DI, Huang B, Gomez-Navarro J and Saltz LB: Phase II study of the anti-cytotoxic T-lymphocyte-associated antigen 4 monoclonal antibody, tremelimumab, in patients with refractory metastatic colorectal cancer. J Clin Oncol. 28:3485–3490. 2010. View Article : Google Scholar

71 

Chalabi M, Fanchi LF, Dijkstra KK, Van den Berg JG, Aalbers AG, Sikorska K, Lopez-Yurda M, Grootscholten C, Beets GL, Snaebjornsson P, et al: Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers. Nat Med. 26:566–576. 2020. View Article : Google Scholar

72 

Herbst RS, Garon EB, Kim DW, Cho BC, Perez-Gracia JL, Han JY, Arvis CD, Majem M, Forster MD, Monnet I, et al: Long-term outcomes and retreatment among patients with previously treated, programmed death-ligand 1-positive, advanced non-small-cell lung cancer in the KEYNOTE-010 study. J Clin Oncol. 38:1580–1590. 2020. View Article : Google Scholar

73 

Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, et al: Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 366:2455–2465. 2012. View Article : Google Scholar

74 

Eng C, Kim TW, Bendell J, Argilés G, Tebbutt NC, Di Bartolomeo M, Falcone A, Fakih M, Kozloff M, Segal NH, et al: Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370): A multicentre, open-label, phase 3, randomised, controlled trial. Lancet Oncol. 20:849–861. 2019. View Article : Google Scholar

75 

Grothey A, Tabernero J, Arnold D, De Gramont A, Ducreux MP, O'Dwyer PJ, Van Cutsem E, Bosanac I, Srock S, Mancao C, et al: Fluoropyrimidine (FP) + bevacizumab (BEV) + atezolizumab vs FP/BEV in BRAFwt metastatic colorectal cancer (mCRC): Findings from Cohort 2 of MODUL-a multicentre, randomized trial of biomarker-driven maintenance treatment following first-line induction therapy. Ann Oncol. 29(Suppl 8): viii714–viii715. 2018. View Article : Google Scholar

76 

Lee JJ, Yothers G, Jacobs SA, Sanoff HK, Cohen DJ, Guthrie KA, Henry NL, Ganz PA, Kopetz S, Lucas PC, et al: Colorectal cancer metastatic dMMR immuno-therapy (COMMIT) study (NRG-GI004/SWOG-S1610): A randomized phase III study of mFOLFOX6/bevacizumab combination chemotherapy with or without atezolizumab or atezolizumab monotherapy in the first-line treatment of patients with deficient DNA mismatch repair (dMMR) metastatic colorectal cancer. J Clin Oncol. 36(Suppl 15): TPS36152018. View Article : Google Scholar

77 

Sinicrope FA, Ou FS, Shi Q, Nixon AB, Mody K, Levasseur A, Dueck AC, Dhanarajan AR, Lieu CH, Cohen DJ, et al: Randomized trial of FOLFOX alone or combined with atezolizumab as adjuvant therapy for patients with stage III colon cancer and deficient DNA mismatch repair or microsatellite instability (ATOMIC, Alliance A021502). J Clin Oncol. 35(Suppl 15): TPS36302017. View Article : Google Scholar

78 

Chiou VL and Burotto M: Pseudoprogression and Immune-Related Response in Solid Tumors. J Clin Oncol. 33:3541–3543. 2015. View Article : Google Scholar

79 

Solinas C, Porcu M, Hlavata Z, De Silva P, Puzzoni M, Willard-Gallo K, Scartozzi M and Saba L: Critical features and challenges associated with imaging in patients undergoing cancer immunotherapy. Crit Rev Oncol Hematol. 120:13–21. 2017. View Article : Google Scholar

80 

Seymour L, Bogaerts J, Perrone A, Ford R, Schwartz LH, Mandrekar S, Lin NU, Litière S, Dancey J, Chen A, et al: iRECIST: Guidelines for response criteria for use in trials testing immunotherapeutics. Lancet Oncol. 18:e143–e152. 2017. View Article : Google Scholar

81 

Ducreux M, Bennouna J, Hebbar M, Ychou M, Lledo G, Conroy T, Adenis A, Faroux R, Rebischung C, Bergougnoux L, et al: Capecitabine plus oxaliplatin (XELOX) versus 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOX-6) as first-line treatment for metastatic colorectal cancer. Int J Cancer. 128:682–690. 2011. View Article : Google Scholar

82 

Overman MJ, Bergamo F, McDermott RS, Aglietta M, Chen F, Gelsomino F, Wong M, Morse M, Van Cutsem E, Hendlisz A, et al: Nivolumab in patients with DNA mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer (mCRC): Long-term survival according to prior line of treatment from CheckMate-142. J Clin Oncol. 36(Suppl 4): S5542018. View Article : Google Scholar

83 

Overman MJ, Lonardi S, Wong KYM, Lenz HJ, Gelsomino F, Aglietta M, Morse MA, Van Cutsem E, McDermott R, Hill A, et al: Durable clinical benefit with nivolumab plus ipilimumab in DNA mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer. J Clin Oncol. 36:773–779. 2018. View Article : Google Scholar

84 

Brahmer JR, Lacchetti C, Schneider BJ, Atkins MB, Brassil KJ, Caterino JM, Chau I, Ernstoff MS, Gardner JM, Ginex P, et al: 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. 36:1714–1768. 2018. View Article : Google Scholar

85 

Woo SR, Turnis ME, Goldberg MV, Bankoti J, Selby M, Nirschl CJ, Bettini ML, Gravano DM, Vogel P, Liu CL, et al: Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Res. 72:917–927. 2012. View Article : Google Scholar

86 

Ngiow SF, von Scheidt B, Akiba H, Yagita H, Teng MW and Smyth MJ: Anti-TIM3 antibody promotes T cell IFN-γ-mediated antitumor immunity and suppresses established tumors. Cancer Res. 71:3540–3551. 2011. View Article : Google Scholar

87 

Anderson AC, Joller N and Kuchroo VK: Lag-3, Tim-3, and TIGIT: Co-inhibitory receptors with specialized functions in immune regulation. Immunity. 44:989–1004. 2016. View Article : Google Scholar

88 

Ward-Kavanagh LK, Lin WW, Šedý JR and Ware CF: The TNF receptor superfamily in co-stimulating and co-inhibitory responses. Immunity. 44:1005–1019. 2016. View Article : Google Scholar

89 

Kroemer G, Galluzzi L, Kepp O and Zitvogel L: Immunogenic cell death in cancer therapy. Annu Rev Immunol. 31:51–72. 2013. View Article : Google Scholar

90 

Sun X, Suo J and Yan J: Immunotherapy in human colorectal cancer: Challenges and prospective. World J Gastroenterol. 22:6362–6372. 2016. View Article : Google Scholar

91 

Ganesh K, Stadler ZK, Cercek A, Mendelsohn RB, Shia J, Segal NH and Diaz LA Jr: Immunotherapy in colorectal cancer: Rationale, challenges and potential. Nat Rev Gastroenterol Hepatol. 16:361–375. 2019. View Article : Google Scholar

92 

Limagne E, Euvrard R, Thibaudin M, Rébé C, Derangère V, Chevriaux A, Boidot R, Végran F, Bonnefoy N, Vincent J, et al: Accumulation of MDSC and Th17 cells in patients with metastatic colorectal cancer predicts the efficacy of a FOLFOX-bevacizumab drug treatment regimen. Cancer Res. 76:5241–5252. 2016. View Article : Google Scholar

93 

Hochster HS, Bendell JC, Cleary JM, Foster P, Zhang W, He X, Hernandez G, Iizuka K and Eckhardt SG: Efficacy and safety of atezolizumab (atezo) and bevacizumab (bev) in a phase Ib study of microsatellite instability (MSI)-high metastatic colorectal cancer (mCRC). J Clin Oncol. 35(Suppl 4): S6732017. View Article : Google Scholar

94 

Kaminski JM, Shinohara E, Summers JB, Niermann KJ, Morimoto A and Brousal J: The controversial abscopal effect. Cancer Treat Rev. 31:159–172. 2005. View Article : Google Scholar

95 

Gaipl US, Multhoff G, Scheithauer H, Lauber K, Hehlgans S, Frey B and Rödel F: Kill and spread the word: Stimulation of antitumor immune responses in the context of radiotherapy. Immunotherapy. 6:597–610. 2014. View Article : Google Scholar

96 

Postow MA, Callahan MK, Barker CA, Yamada Y, Yuan J, Kitano S, Mu Z, Rasalan T, Adamow M, Ritter E, et al: Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med. 366:925–931. 2012. View Article : Google Scholar

97 

Segal NH, Kemeny NE, Cercek A, Reidy DL, Raasch PJ, War ren P, Hrabovsky AE, Campbell N, Shia J, Goodman KA, et al: Non-randomized phase II study to assess the efficacy of pembrolizumab (Pem) plus radiotherapy (RT) or ablation in mismatch repair proficient (pMMR) metastatic colorectal cancer (mCRC) patients. J Clin Oncol. 34(Suppl 15): S35392016. View Article : Google Scholar

98 

Lee JJ, Yothers G, George TJ, Fakih MG, Mallick AB, Mitchell EP, Wade JL, Krauss JC, Kayaleh OR, Heron DE, et al: Abstract 2257: Phase II study of dual immune checkpoint blockade (ICB) with durvalumab (Durva) plus tremelimumab (T) following palliative hypofractionated radiotherapy (SBRT) in patients (pts) with microsatellite-stable (MSS) metastatic colorectal cancer (mCRC) progressing on chemotherapy: NSABP FC-9. Cancer Res. 79(Suppl 13): S22572019.

99 

O'Donnell JS, Long GV, Scolyer RA, Teng MWL and Smyth MJ: Resistance to PD1/PDL1 checkpoint inhibition. Cancer Treat Rev. 52:71–81. 2017. View Article : Google Scholar

100 

Chen DS and Mellman I: Elements of cancer immunity and the cancer-immune set point. Nature. 541:321–330. 2017. View Article : Google Scholar

101 

Hugo W, Zaretsky JM, Sun L, Song C, Moreno BH, Hu-Lieskovan S, Berent-Maoz B, Pang J, Chmielowski B, Cherry G, et al: Genomic and transcriptomic features of response to anti-PD-1 therapy in metastatic melanoma. Cell. 165:35–44. 2016. View Article : Google Scholar

102 

O'Neil BH, Wallmark JM, Lorente D, Elez E, Raimbourg J, Gomez-Roca C, Ejadi S, Piha-Paul SA, Stein MN, Abdul Razak AR, et al: Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with advanced colorectal carcinoma. PLoS One. 12:e01898482017. View Article : Google Scholar

103 

Kopetz S, Andre T, Overman MJ, Zagonel V, Lonardi S, Aglietta M, Gelsomino F, McDermott R, Wong KYM, Hendlisz A, et al: Abstract 2603: Exploratory analysis of Janus kinase 1 (JAK1) loss-of-function (LoF) mutations in patients with DNA mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer (mCRC) treated with nivolumab + ipilimumab in CheckMate-142. Cancer Res. 78(Suppl 13): S26032018.

104 

Zaretsky JM, Garcia-Diaz A, Shin DS, Escuin-Ordinas H, Hugo W, Hu-Lieskovan S, Torrejon DY, Abril-Rodriguez G, Sandoval S, Barthly L, et al: Mutations associated with acquired resistance to PD-1 blockade in melanoma. N Engl J Med. 375:819–829. 2016. View Article : Google Scholar

105 

Llosa NJ, Luber B, Siegel N, Awan AH, Oke T, Zhu Q, Bartlett BR, Aulakh LK, Thompson ED, Jaffee EM, et al: Immunopathologic stratification of colorectal cancer for checkpoint blockade immunotherapy. Cancer Immunol Res. 7:1574–1579. 2019. View Article : Google Scholar

106 

Chen YP, Zhang Y, Lv JW, Li YQ, Wang YQ, He QM, Yang XJ, Sun Y, Mao YP, Yun JP, et al: Genomic analysis of tumor microenvironment immune types across 14 solid cancer types: Immunotherapeutic implications. Theranostics. 7:3585–3594. 2017. View Article : Google Scholar

107 

Sun C, Mezzadra R and Schumacher TN: Regulation and function of the PD-L1 checkpoint. Immunity. 48:434–452. 2018. View Article : Google Scholar

108 

Daassi D, Mahoney KM and Freeman GJ: The importance of exosomal PDL1 in tumour immune evasion. Nat Rev Immunol. 20:209–215. 2020. View Article : Google Scholar

109 

Li XY, Das I, Lepletier A, Addala V, Bald T, Stannard K, Barkauskas D, Liu J, Aguilera AR, Takeda K, et al: CD155 loss enhances tumor suppression via combined host and tumor-intrinsic mechanisms. J Clin Invest. 128:2613–2625. 2018. View Article : Google Scholar

110 

Blake SJ, Stannard K, Liu J, Allen S, Yong MC, Mittal D, Aguilera AR, Miles JJ, Lutzky VP, de Andrade LF, et al: Suppression of metastases using a new lymphocyte checkpoint target for cancer immunotherapy. Cancer Discov. 6:446–459. 2016. View Article : Google Scholar

111 

Harjunpää H, Blake SJ, Ahern E, Allen S, Liu J, Yan J, Lutzky V, Takeda K, Aguilera AR, Guillerey C, et al: Deficiency of host CD96 and PD-1 or TIGIT enhances tumor immunity without significantly compromising immune homeostasis. OncoImmunology. 7:e14459492018. View Article : Google Scholar

112 

Neubert NJ, Schmittnaegel M, Bordry N, Nassiri S, Wald N, Martignier C, Tillé L, Homicsko K, Damsky W, Maby-El Hajjami H, et al: T cell-induced CSF1promotes melanoma resistance to PD1 blockade. Sci Transl Med. 10:eaan33112018. View Article : Google Scholar

113 

Seliger B: The link between MHC class I abnormalities of tumors, oncogenes, tumor suppressor genes, and transcription factors. J Immunotoxicol. 11:308–310. 2014. View Article : Google Scholar

114 

Godfrey DI, Le Nours J, Andrews DM, Uldrich AP and Rossjohn J: Unconventional T cell targets for cancer immunotherapy. Immunity. 48:453–473. 2018. View Article : Google Scholar

115 

Sade-Feldman M, Jiao YJ, Chen JH, Rooney MS, Barzily-Rokni M, Eliane JP, Bjorgaard SL, Hammond MR, Vitzthum H, Blackmon SM, et al: Resistance to checkpoint blockade therapy through inactivation of antigen presentation. Nat Commun. 8:11362017. View Article : Google Scholar

116 

Takeda K, Nakayama M, Hayakawa Y, Kojima Y, Ikeda H, Imai N, Ogasawara K, Okumura K, Thomas DM and Smyth MJ: IFN-γ is required for cytotoxic T cell-dependent cancer genome immunoediting. Nat Commun. 8:146072017. View Article : Google Scholar

117 

Dunn GP, Ikeda H, Bruce AT, Koebel C, Uppaluri R, Bui J, Chan R, Diamond M, White JM, Sheehan KC and Schreiber RD: Interferon-gamma and cancer immunoediting. Immunol Res. 32:231–245. 2005. View Article : Google Scholar

118 

Gao J, Shi LZ, Zhao H, Chen J, Xiong L, He Q, Chen T, Roszik J, Bernatchez C, Woodman SE, et al: Loss of IFN-γ pathway genes in tumor cells as a mechanism of resistance to anti-CTLA-4 therapy. Cell. 167:397–404.e9. 2016. View Article : Google Scholar

119 

Kearney CJ, Vervoort SJ, Hogg SJ, Ramsbottom KM, Freeman AJ, Lalaoui N, Pijpers L, Michie J, Brown KK, Knight DA, et al: Tumor immune evasion arises through loss of TNF sensitivity. Sci Immunol 3: eaar3451,. 2018.

120 

Vijayan D, Young A, Teng MWL and Smyth MJ: Targeting immunosuppressive adenosine in cancer. Nat Rev Cancer. 17:709–724. 2017. View Article : Google Scholar

121 

Ohta A, Gorelik E, Prasad SJ, Ronchese F, Lukashev D, Wong MK, Huang X, Caldwell S, Liu K, Smith P, et al: A2A adenosine receptor protects tumors from antitumor T cells. Proc Natl Acad Sci USA. 103:13132–13137. 2006. View Article : Google Scholar

122 

Beavis PA, Divisekera U, Paget C, Chow MT, John LB, Devaud C, Dwyer K, Stagg J, Smyth MJ and Darcy PK: Blockade of A2A receptors potently suppresses the metastasis of CD73+ tumors. Proc Natl Acad Sci USA. 110:14711–14716. 2013. View Article : Google Scholar

123 

Chen L, Diao L, Yang Y, Yi X, Rodriguez BL, Li Y, Villalobos PA, Cascone T, Liu X, Tan L, et al: CD38-mediated immunosuppression as a mechanism of tumor cell escape from PD-1/PD-L1 blockade. Cancer Discov. 8:1156–1175. 2018. View Article : Google Scholar

124 

Triplett TA, Garrison KC, Marshall N, Donkor M, Blazeck J, Lamb C, Qerqez A, Dekker JD, Tanno Y, Lu WC, et al: Reversal of indoleamine 2,3-dioxygenase-mediated cancer immune suppression by systemic kynurenine depletion with a therapeutic enzyme. Nat Biotechnol. 36:758–764. 2018. View Article : Google Scholar

125 

Moon YW, Hajjar J, Hwu P and Naing A: Targeting the indoleamine 2,3-dioxygenase pathway in cancer. J Immunother Cancer. 3:512015. View Article : Google Scholar

126 

Voron T, Colussi O, Marcheteau E, Pernot S, Nizard M, Point AL, Latreche S, Bergaya S, Benhamouda N, Tanchot C, et al: VEGF-A modulates expression of inhibitory checkpoints on CD8+ T cells in tumors. J Exp Med. 212:139–148. 2015. View Article : Google Scholar

127 

Johnston CJ, Smyth DJ, Dresser DW and Maizels RM: TGF-β in tolerance, development and regulation of immunity. Cell Immunol. 299:14–22. 2016. View Article : Google Scholar

128 

Strauss J, Heery CR, Schlom J, Madan RA, Cao L, Kang Z, Lamping E, Marté JL, Donahue RN, Grenga I, et al: Phase I trial of M7824 (MSB0011359C), a bifunctional fusion protein targeting PD-L1 and TGFβ, in advanced solid tumors. Clin Cancer Res. 24:1287–1295. 2018. View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Choucair K, Radford M, Bansal A, Park R and Saeed A: Advances in immune therapies for the treatment of microsatellite instability‑high/deficient mismatch repair metastatic colorectal cancer (Review). Int J Oncol 59: 74, 2021.
APA
Choucair, K., Radford, M., Bansal, A., Park, R., & Saeed, A. (2021). Advances in immune therapies for the treatment of microsatellite instability‑high/deficient mismatch repair metastatic colorectal cancer (Review). International Journal of Oncology, 59, 74. https://doi.org/10.3892/ijo.2021.5254
MLA
Choucair, K., Radford, M., Bansal, A., Park, R., Saeed, A."Advances in immune therapies for the treatment of microsatellite instability‑high/deficient mismatch repair metastatic colorectal cancer (Review)". International Journal of Oncology 59.3 (2021): 74.
Chicago
Choucair, K., Radford, M., Bansal, A., Park, R., Saeed, A."Advances in immune therapies for the treatment of microsatellite instability‑high/deficient mismatch repair metastatic colorectal cancer (Review)". International Journal of Oncology 59, no. 3 (2021): 74. https://doi.org/10.3892/ijo.2021.5254
Copy and paste a formatted citation
x
Spandidos Publications style
Choucair K, Radford M, Bansal A, Park R and Saeed A: Advances in immune therapies for the treatment of microsatellite instability‑high/deficient mismatch repair metastatic colorectal cancer (Review). Int J Oncol 59: 74, 2021.
APA
Choucair, K., Radford, M., Bansal, A., Park, R., & Saeed, A. (2021). Advances in immune therapies for the treatment of microsatellite instability‑high/deficient mismatch repair metastatic colorectal cancer (Review). International Journal of Oncology, 59, 74. https://doi.org/10.3892/ijo.2021.5254
MLA
Choucair, K., Radford, M., Bansal, A., Park, R., Saeed, A."Advances in immune therapies for the treatment of microsatellite instability‑high/deficient mismatch repair metastatic colorectal cancer (Review)". International Journal of Oncology 59.3 (2021): 74.
Chicago
Choucair, K., Radford, M., Bansal, A., Park, R., Saeed, A."Advances in immune therapies for the treatment of microsatellite instability‑high/deficient mismatch repair metastatic colorectal cancer (Review)". International Journal of Oncology 59, no. 3 (2021): 74. https://doi.org/10.3892/ijo.2021.5254
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