The Emergence of Immune-checkpoint Inhibitors in Colorectal Cancer Therapy | Bentham Science
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Review Article

The Emergence of Immune-checkpoint Inhibitors in Colorectal Cancer Therapy

Author(s): Michele Ghidini*, Nicola Fusco, Massimiliano Salati, Shelize Khakoo, Gianluca Tomasello, Fausto Petrelli, Dario Trapani and Angelica Petrillo

Volume 22, Issue 9, 2021

Published on: 04 February, 2021

Page: [1021 - 1033] Pages: 13

DOI: 10.2174/1389450122666210204204415

Price: $65

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Abstract

Immunotherapy has revolutionized the treatment landscape in a number of solid tumors. In colorectal cancer, evidence suggests that microsatellite high (MSI-H) tumors are the most responsive to immune checkpoint blockade due to increased neo-antigen load and a favorable tumor microenvironment. Indeed, Pembrolizumab now represents a first-line option in such patients. However, MSI-H tumors represent the minority and a proportion of patients’ progress despite initially responding. Trials are investigating different immunotherapy combinatorial strategies to enhance immune response in less immunogenic colorectal tumors. Such strategies include dual immune checkpoint blockade, combining immune checkpoint inhibitors with other treatment modalities such as radiotherapy, chemotherapy or other biological or targeted agents. Moreover, there is an increasing drive to identify biomarkers to better select patients most likely to respond to immunotherapy and understand intrinsic and acquired resistance mechanisms. Apart from MSI-H tumors, there is a strong rationale to suggest that tumors with alterations in DNA polymerase epsilon and DNA polymerase delta are also likely to respond to immunotherapy and trials in this subpopulation are underway. Other strategies such as priming O6-methylguanineDNA methyltransferase silenced tumors with alkylating agents to make them receptive to immune checkpoint blockade are also being investigated. Here we discuss different colorectal subpopulations together with their likelihood of response to immune checkpoint blockade and strategies to overcome barriers to a successful clinical outcome. We summarize evidence from published clinical trials and provide an overview of trials in progress whilst discussing newer immunotherapy strategies such as adoptive cell therapies and cancer vaccines.

Keywords: Colorectal cancer, immunotherapy, immune-checkpoint inhibitors, microsatellite stable, adoptive cell therapies, cancer vaccines.

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[1]
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, 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.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[2]
Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut 2017; 66(4): 683-91.
[http://dx.doi.org/10.1136/gutjnl-2015-310912] [PMID: 26818619]
[3]
Dekker E, Tanis PJ, Vleugels JLA, Kasi PM, Wallace MB. Colorectal cancer. Lancet 2019; 394(10207): 1467-80.
[http://dx.doi.org/10.1016/S0140-6736(19)32319-0] [PMID: 31631858]
[4]
Georgiou A, Khakoo S, Edwards P, et al. Outcomes of patients with early onset colorectal cancer treated in a uk specialist cancer center. Cancers 2019; 11: 1558.https://www.mdpi.com/552754
[http://dx.doi.org/10.3390/cancers11101558]
[5]
Araghi M, Soerjomataram I, Bardot A, et al. Changes in colorectal cancer incidence in seven high-income countries: a population-based study. Lancet Gastroenterol Hepatol 2019; 4(7): 511-8.
[http://dx.doi.org/10.1016/S2468-1253(19)30147-5] [PMID: 31105047]
[6]
American Cancer Society. Colorectal Cancer Facts & Figures 2020-2022. 2020.https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/colorectal-cancer-facts-and-figures/colorectal-cancer-facts-and-figures-2020-2022.pdf
[7]
Nagtegaal ID, Odze RD, Klimstra D, et al. The 2019 WHO classification of tumours of the digestive system. Histopathology 2020; 76(2): 182-8.
[http://dx.doi.org/10.1111/his.13975] [PMID: 31433515]
[8]
Compton CC, Fielding LP, Burgart LJ, et al. Prognostic factors in colorectal cancer. College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med 2000; 124(7): 979-94.
[PMID: 10888773]
[9]
Verhulst J, Ferdinande L, Demetter P, Ceelen W. Mucinous subtype as prognostic factor in colorectal cancer: a systematic review and meta-analysis. J Clin Pathol 2012; 65(5): 381-8.
[http://dx.doi.org/10.1136/jclinpath-2011-200340] [PMID: 22259177]
[10]
Alexander J, Watanabe T, Wu T-T, Rashid A, Li S, Hamilton SR. Histopathological identification of colon cancer with microsatellite instability. Am J Pathol 2001; 158(2): 527-35.
[http://dx.doi.org/10.1016/S0002-9440(10)63994-6] [PMID: 11159189]
[11]
Setaffy L, Langner C. Microsatellite instability in colorectal cancer: clinicopathological significance. Pol J Pathol 2015; 66(3): 203-18.
[http://dx.doi.org/10.5114/pjp.2015.54953] [PMID: 26619098]
[12]
Guinney J, Dienstmann R, Wang X, et al. The consensus molecular subtypes of colorectal cancer. Nat Med 2015; 21(11): 1350-6.
[http://dx.doi.org/10.1038/nm.3967] [PMID: 26457759]
[13]
Loree JM, Pereira AAL, Lam M, et al. Classifying colorectal cancer by tumor location rather than sidedness highlights a continuum in mutation profiles and consensus molecular subtypes. Clin Cancer Res 2018; 24(5): 1062-72.
[http://dx.doi.org/10.1158/1078-0432.CCR-17-2484] [PMID: 29180604]
[14]
Karpinski P, Rossowska J, Sasiadek MM. Immunological landscape of consensus clusters in colorectal cancer. Oncotarget 2017; 8(62): 105299-311.
[http://dx.doi.org/10.18632/oncotarget.22169] [PMID: 29285252]
[15]
Schumacher TN, Schreiber RD. Neoantigens in cancer immunotherapy. Science (80- ) 2015; 348(6230): 69-74.
[http://dx.doi.org/10.1126/science.aaa4971]
[16]
Picard E, Verschoor CP, Ma GW, Pawelec G. Relationships between immune landscapes, genetic subtypes and responses to immunotherapy in colorectal cancer. Front Immunol 2020; 11: 369.
[http://dx.doi.org/10.3389/fimmu.2020.00369] [PMID: 32210966]
[17]
Rayner E, van Gool IC, Palles C, et al. A panoply of errors: polymerase proofreading domain mutations in cancer. Nat Rev Cancer 2016; 16(2): 71-81.
[http://dx.doi.org/10.1038/nrc.2015.12] [PMID: 26822575]
[18]
Becht E, de Reyniès A, Giraldo NA, et al. Immune and stromal classification of colorectal cancer is associated with molecular subtypes and relevant for precision immunotherapy. Clin Cancer Res 2016; 22(16): 4057-66.
[http://dx.doi.org/10.1158/1078-0432.CCR-15-2879] [PMID: 26994146]
[19]
Jass JR. Classification of colorectal cancer based on correlation of clinical, morphological and molecular features. Histopathology 2007; 50(1): 113-30.
[http://dx.doi.org/10.1111/j.1365-2559.2006.02549.x] [PMID: 17204026]
[20]
Ogino S, Goel A. Molecular classification and correlates in colorectal cancer. J Mol Diagn 2008; 10(1): 13-27.
[http://dx.doi.org/10.2353/jmoldx.2008.070082] [PMID: 18165277]
[21]
De Sousa E Melo F, Wang X, Jansen M, et al. Poor-prognosis colon cancer is defined by a molecularly distinct subtype and develops from serrated precursor lesions. Nat Med 2013; 19(5): 614-8.
[http://dx.doi.org/10.1038/nm.3174] [PMID: 23584090]
[22]
Sadanandam A, Lyssiotis CA, Homicsko K, et al. A colorectal cancer classification system that associates cellular phenotype and responses to therapy. Nat Med 2013; 19(5): 619-25.
[http://dx.doi.org/10.1038/nm.3175] [PMID: 23584089]
[23]
Marisa L, de Reyniès A, Duval A, et al. Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value. In: Kemp C, editor PLoS Med 2013; 10(5): e1001453.
[24]
Roepman P, Schlicker A, Tabernero J, et al. Colorectal cancer intrinsic subtypes predict chemotherapy benefit, deficient mismatch repair and epithelial-to-mesenchymal transition. Int J Cancer 2014; 134(3): 552-62.
[http://dx.doi.org/10.1002/ijc.28387] [PMID: 23852808]
[25]
Dunne PD, Alderdice M, O’Reilly PG, et al. Cancer-cell intrinsic gene expression signatures overcome intratumoural heterogeneity bias in colorectal cancer patient classification. Nat Commun 2017; 8(1): 15657.
[http://dx.doi.org/10.1038/ncomms15657] [PMID: 28561046]
[26]
Khakoo S, Moorcraft S, Pacis A, et al. P-138 A comparison of the transcriptomic profiles of matched tissue from primary colorectal cancer and corresponding secondary lung metastases. Ann Oncol 2020; 31: S134-5.
[http://dx.doi.org/10.1016/j.annonc.2020.04.220]
[27]
Isella C, Terrasi A, Bellomo SE, et al. Stromal contribution to the colorectal cancer transcriptome. Nat Genet 2015; 47(4): 312-9.
[http://dx.doi.org/10.1038/ng.3224] [PMID: 25706627]
[28]
Trumpi K, Ubink I, Trinh A, et al. Neoadjuvant chemotherapy affects molecular classification of colorectal tumors. Oncogenesis 2017; 6(7): e357-7.
[http://dx.doi.org/10.1038/oncsis.2017.48] [PMID: 28692036]
[29]
Woolston A, Khan K, Spain G, et al. Genomic and transcriptomic determinants of therapy resistance and immune landscape evolution during anti-egfr treatment in colorectal cancer. Cancer Cell 2019; 36(1): 35-50.e9.
[http://dx.doi.org/10.1016/j.ccell.2019.05.013] [PMID: 31287991]
[30]
Belli C, Trapani D, Viale G, et al. Targeting the microenvironment in solid tumors. Cancer Treat Rev 2018; 65: 22-32.
[http://dx.doi.org/10.1016/j.ctrv.2018.02.004] [PMID: 29502037]
[31]
Golshani G, Zhang Y. Advances in immunotherapy for colorectal cancer: a review. Therap Adv Gastroenterol 2020; 13: 1756284820917527.
[http://dx.doi.org/10.1177/1756284820917527] [PMID: 32536977]
[32]
Thomas J, Leal A, Overman MJ. Clinical development of immunotherapy for deficient mismatch repair colorectal cancer. Clin Colorectal Cancer 2020; 19(2): 73-81.
[http://dx.doi.org/10.1016/j.clcc.2020.02.002] [PMID: 32173280]
[33]
Cohen R, Rousseau B, Vidal J, Colle R, Diaz LA Jr, André T. Immune checkpoint inhibition in colorectal cancer: microsatellite instability and beyond. Target Oncol 2020; 15(1): 11-24.
[http://dx.doi.org/10.1007/s11523-019-00690-0] [PMID: 31786718]
[34]
Ganesh K, Stadler ZK, Cercek A, et al. Immunotherapy in colorectal cancer: rationale, challenges and potential. Nat Rev Gastroenterol Hepatol 2019; 16(6): 361-75.
[http://dx.doi.org/10.1038/s41575-019-0126-x] [PMID: 30886395]
[35]
Battaglin F, Naseem M, Lenz H-J, Salem ME. Microsatellite instability in colorectal cancer: overview of its clinical significance and novel perspectives. Clin Adv Hematol Oncol 2018; 16(11): 735-45.
[PMID: 30543589]
[36]
Nojadeh JN, Behrouz Sharif S, Sakhinia E. Microsatellite instability in colorectal cancer. EXCLI J 2018; 17: 159-68.
[PMID: 29743854]
[37]
Corti C, Sajjadi E, Fusco N. Determination of mismatch repair status in human cancer and its clinical significance: does one size fit all? Adv Anat Pathol 2019; 26(4): 270-9.
[http://dx.doi.org/10.1097/PAP.0000000000000234] [PMID: 30932972]
[38]
Gupta D, Heinen CD. The mismatch repair-dependent DNA damage response: Mechanisms and implications. DNA Repair (Amst) 2019; 78: 60-9.
[http://dx.doi.org/10.1016/j.dnarep.2019.03.009] [PMID: 30959407]
[39]
Li Z, Pearlman AH, Hsieh P. DNA mismatch repair and the DNA damage response. DNA Repair (Amst) 2016; 38: 94-101.
[http://dx.doi.org/10.1016/j.dnarep.2015.11.019] [PMID: 26704428]
[40]
Fusco N, Lopez G, Corti C, et al. Mismatch repair protein loss as a prognostic and predictive biomarker in breast cancers regardless of microsatellite instability. JNCI Cancer Spectr 2018; 2(4)
[http://dx.doi.org/10.1093/jncics/pky056]
[41]
Catalano I, Grassi E, Bertotti A, Trusolino L. Immunogenomics of colorectal tumors: facts and hypotheses on an evolving saga. Trends Cancer 2019; 5(12): 779-88.
[http://dx.doi.org/10.1016/j.trecan.2019.10.006] [PMID: 31813455]
[42]
Chen C, Liu S, Qu R, Li B. Recurrent neoantigens in colorectal cancer as potential immunotherapy targets. BioMed Res Int 2020; 2020: 2861240.
[http://dx.doi.org/10.1155/2020/2861240] [PMID: 32733937]
[43]
Chalmers ZR, Connelly CF, Fabrizio D, et al. Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med 2017; 9(1): 34.
[http://dx.doi.org/10.1186/s13073-017-0424-2] [PMID: 28420421]
[44]
Noh B-J, Kwak JY, Eom D-W. Immune classification for the PD-L1 expression and tumour-infiltrating lymphocytes in colorectal adenocarcinoma. BMC Cancer 2020; 20(1): 58.
[http://dx.doi.org/10.1186/s12885-020-6553-9] [PMID: 31992245]
[45]
Kong P, Wang J, Song Z, et al. Circulating lymphocytes, pd-l1 expression on tumor-infiltrating lymphocytes, and survival of colorectal cancer patients with different mismatch repair gene status. J Cancer 2019; 10(7): 1745-54.
[http://dx.doi.org/10.7150/jca.25187] [PMID: 31205530]
[46]
Sahin IH, Akce M, Alese O, et al. Immune checkpoint inhibitors for the treatment of MSI-H/MMR-D colorectal cancer and a perspective on resistance mechanisms. Br J Cancer 2019; 121(10): 809-18.
[http://dx.doi.org/10.1038/s41416-019-0599-y] [PMID: 31607751]
[47]
Fancello L, Gandini S, Pelicci PG, Mazzarella L. Tumor mutational burden quantification from targeted gene panels: major advancements and challenges. J Immunother Cancer 2019; 7(1): 183.
[http://dx.doi.org/10.1186/s40425-019-0647-4] [PMID: 31307554]
[48]
Galuppini F, Dal Pozzo CA, Deckert J, Loupakis F, Fassan M, Baffa R. Tumor mutation burden: from comprehensive mutational screening to the clinic. Cancer Cell Int 2019; 19(1): 209.
[http://dx.doi.org/10.1186/s12935-019-0929-4] [PMID: 31406485]
[49]
Pagni F, Guerini-Rocco E, Schultheis AM, et al. Targeting immune-related biological processes in solid tumors: we do need biomarkers. Int J Mol Sci 2019; 20(21): 5452.
[http://dx.doi.org/10.3390/ijms20215452] [PMID: 31683784]
[50]
McGranahan N, Furness AJS, Rosenthal R, et al. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science (80- ) 2016; 351(6280): 1463-9.
[http://dx.doi.org/10.1126/science.aaf1490]
[51]
Fumet J-D, Truntzer C, Yarchoan M, Ghiringhelli F. Tumour mutational burden as a biomarker for immunotherapy: Current data and emerging concepts. Eur J Cancer 2020; 131: 40-50.
[http://dx.doi.org/10.1016/j.ejca.2020.02.038] [PMID: 32278982]
[52]
Stenzinger A, Allen JD, Maas J, et al. Tumor mutational burden standardization initiatives: Recommendations for consistent tumor mutational burden assessment in clinical samples to guide immunotherapy treatment decisions. Genes Chromosomes Cancer 2019; 58(8): 578-88.
[http://dx.doi.org/10.1002/gcc.22733] [PMID: 30664300]
[53]
Schrock AB, Ouyang C, Sandhu J, et al. Tumor mutational burden is predictive of response to immune checkpoint inhibitors in MSI-high metastatic colorectal cancer. Ann Oncol 2019; 30(7): 1096-103.
[http://dx.doi.org/10.1093/annonc/mdz134] [PMID: 31038663]
[54]
Pietrantonio F, de Braud F, Milione M, et al. Dose-dense temozolomide in patients with mgmt-silenced chemorefractory colorectal cancer. Target Oncol 2016; 11(3): 337-43.
[http://dx.doi.org/10.1007/s11523-015-0397-2] [PMID: 26538496]
[55]
Pietrantonio F, Perrone F, de Braud F, et al. Activity of temozolomide in patients with advanced chemorefractory colorectal cancer and MGMT promoter methylation. Ann Oncol 2014; 25(2): 404-8.
[http://dx.doi.org/10.1093/annonc/mdt547] [PMID: 24379162]
[56]
van Nifterik KA, van den Berg J, van der Meide WF, et al. Absence of the MGMT protein as well as methylation of the MGMT promoter predict the sensitivity for temozolomide. Br J Cancer 2010; 103(1): 29-35.
[http://dx.doi.org/10.1038/sj.bjc.6605712] [PMID: 20517307]
[57]
Schwartz S, Szeto C, Tian Y, et al. Refining the selection of patients with metastatic colorectal cancer for treatment with temozolomide using proteomic analysis of O6-methylguanine-DNA-methyltransferase. Eur J Cancer 2019; 107: 164-74.
[http://dx.doi.org/10.1016/j.ejca.2018.11.016] [PMID: 30579113]
[58]
Inno A, Fanetti G, Di Bartolomeo M, et al. Role of MGMT as biomarker in colorectal cancer. World J Clin Cases 2014; 2(12): 835-9.
[http://dx.doi.org/10.12998/wjcc.v2.i12.835] [PMID: 25516857]
[59]
Pietrantonio F, Randon G, Romagnoli D, Di Donato S, Benelli M, de Braud F. Biomarker-guided implementation of the old drug temozolomide as a novel treatment option for patients with metastatic colorectal cancer. Cancer Treat Rev 2020; 82: 101935.
[http://dx.doi.org/10.1016/j.ctrv.2019.101935] [PMID: 31821983]
[60]
Gong J, Wang C, Lee PP, Chu P, Fakih M. Response to pd-1 blockade in microsatellite stable metastatic colorectal cancer harboring a pole mutation. J Natl Compr Canc Netw 2017; 15(2): 142-7.
[http://dx.doi.org/10.6004/jnccn.2017.0016] [PMID: 28188185]
[61]
Guerra J, Pinto C, Pinto D, et al. POLE somatic mutations in advanced colorectal cancer. Cancer Med 2017; 6(12): 2966-71.
[http://dx.doi.org/10.1002/cam4.1245] [PMID: 29072370]
[62]
Nebot-Bral L, Brandao D, Verlingue L, et al. Hypermutated tumours in the era of immunotherapy: The paradigm of personalised medicine. Eur J Cancer 2017; 84: 290-303.
[http://dx.doi.org/10.1016/j.ejca.2017.07.026] [PMID: 28846956]
[63]
Domingo E, Freeman-Mills L, Rayner E, et al. Somatic POLE proofreading domain mutation, immune response, and prognosis in colorectal cancer: a retrospective, pooled biomarker study. Lancet Gastroenterol Hepatol 2016; 1(3): 207-16.
[http://dx.doi.org/10.1016/S2468-1253(16)30014-0] [PMID: 28404093]
[64]
Brahmer JR, Drake CG, Wollner I, 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 2010; 28(19): 3167-75.
[http://dx.doi.org/10.1200/JCO.2009.26.7609] [PMID: 20516446]
[65]
Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science (80- ) 2017; 357(6349): 409-13.
[66]
Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 2015; 372(26): 2509-20.
[http://dx.doi.org/10.1056/NEJMoa1500596] [PMID: 26028255]
[67]
Overman MJ, McDermott R, Leach JL, 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 2017; 18(9): 1182-91.
[http://dx.doi.org/10.1016/S1470-2045(17)30422-9] [PMID: 28734759]
[68]
U.S. Food and Drug Administration. FDA grants nivolumab accelerated approval for MSI-H or dMMR colorectal cancer | FDA. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-nivolumab-accelerated-approval-msi-h-or-dmmr-colorectal-cancer
[69]
Andre T, Shiu K-K, Kim TW, et al. Pembrolizumab versus chemotherapy for microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer: The phase 3 KEYNOTE-177 Study. J Clin Oncol 2020; 38(18): LBA4-4.
[70]
U.S. Food and Drug Administration. FDA approves pembrolizumab for first-line treatment of MSI-H/dMMR colorectal cancer | FDA. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-pembrolizumab-first-line-treatment-msi-hdmmr-colorectal-cancer#:~:text=On2020.
[71]
Overman MJ, Lonardi S, Wong KYM, et al. Durable clinical benefit with nivolumab plus ipilimumab in dna mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer. J Clin Oncol 2018; 36(8): 773-9.
[http://dx.doi.org/10.1200/JCO.2017.76.9901] [PMID: 29355075]
[72]
Lenz H-JJ, Van Cutsem E, Limon ML, 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 2018; 8: VIII714.
[73]
Morse MA, Overman MJ, Hartman L, et al. Safety of nivolumab plus low-dose ipilimumab in previously treated microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer. Oncologist 2019; 24(11): 1453-61.
[http://dx.doi.org/10.1634/theoncologist.2019-0129] [PMID: 31147488]
[74]
National Cancer Institute. Immunotherapy combination approved for colorectal cancer. https://www.cancer.gov/news-events/cancer-currents-blog/2018/fda-ipilimumab-nivolumab-colorectal-dna-repair#:~:text=On
[75]
Chen EX, Jonker DJ, Loree JM, et al. 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): 831-8.
[http://dx.doi.org/10.1001/jamaoncol.2020.0910] [PMID: 32379280]
[76]
Corcoran RB, Grothey A. Efficacy of immunotherapy in microsatellite-stable or mismatch repair proficient colorectal cancer-fact or fiction? JAMA Oncol 2020; 6(6): 823-4.
[http://dx.doi.org/10.1001/jamaoncol.2020.0504] [PMID: 32379270]
[77]
Napolitano S, Matrone N, Muddassir AL, et al. Triple blockade of EGFR, MEK and PD-L1 has antitumor activity in colorectal cancer models with constitutive activation of MAPK signaling and PD-L1 overexpression. J Exp Clin Cancer Res 2019; 38(1): 492.
[http://dx.doi.org/10.1186/s13046-019-1497-0] [PMID: 31842958]
[78]
Hellmann MD, Kim T-W, Lee CB, et al. Phase Ib study of atezolizumab combined with cobimetinib in patients with solid tumors. Ann Oncol 2019; 30(7): 1134-42.
[http://dx.doi.org/10.1093/annonc/mdz113] [PMID: 30918950]
[79]
Eng C, Kim TW, Bendell J, 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 2019; 20(6): 849-61.
[http://dx.doi.org/10.1016/S1470-2045(19)30027-0] [PMID: 31003911]
[80]
Antoniotti C, Borelli B, Rossini D, et al. AtezoTRIBE: a randomised phase II study of FOLFOXIRI plus bevacizumab alone or in combination with atezolizumab as initial therapy for patients with unresectable metastatic colorectal cancer. BMC Cancer 2020; 20(1): 683.
[http://dx.doi.org/10.1186/s12885-020-07169-6] [PMID: 32698790]
[81]
Troiani T, Martinelli E, Ciardiello D, et al. Phase II study of avelumab in combination with cetuximab in pre-treated RAS wild-type metastatic colorectal cancer patients: CAVE (cetuximab-avelumab) Colon. J Clin Oncol 2019; 37(4): TPS731-1.
[82]
Marconi R, Strolin S, Bossi G, Strigari L. A meta-analysis of the abscopal effect in preclinical models: Is the biologically effective dose a relevant physical trigger? Woloschak GE, editor PLoS One. 2017; 12: p. (2)e0171559.
[83]
de Rosa N, Rodriguez-Bigas MA, Chang GJ, et al. DNA mismatch repair deficiency in rectal cancer: benchmarking its impact on prognosis, neoadjuvant response prediction, and Clinical Cancer Genetics. J Clin Oncol 2016; 34(25): 3039-46.
[http://dx.doi.org/10.1200/JCO.2016.66.6826] [PMID: 27432916]
[84]
Salem ME, Bodor JN, Puccini A, et al. Relationship between MLH1, PMS2, MSH2 and MSH6 gene-specific alterations and tumor mutational burden in 1057 microsatellite instability-high solid tumors. Int J Cancer 2020; 147(10): 2948-56.
[http://dx.doi.org/10.1002/ijc.33115] [PMID: 32449172]
[85]
Chen EX, Jonker DJ, Loree JM, Kennecke HF, Berry SR, Couture F, et al. CCTG CO.26: Updated analysis and impact of plasma-detected microsatellite stability (MSS) and tumor mutation burden (TMB) in a phase II trial of durvalumab (D) plus tremelimumab (T) and best supportive care (BSC) versus BSC alone in patients (pts) with re. J Clin Oncol 2019; 37(15): 3512-2.
[86]
Chalabi M, Fanchi LF, Dijkstra KK, et al. Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers. Nat Med 2020; 26(4): 566-76.
[http://dx.doi.org/10.1038/s41591-020-0805-8] [PMID: 32251400]
[87]
Fukuoka S, Hara H, Takahashi N, et al. Regorafenib Plus Nivolumab in Patients With Advanced Gastric or Colorectal Cancer: An Open-Label, Dose-Escalation, and Dose-Expansion Phase Ib Trial (REGONIVO, EPOC1603). J Clin Oncol 2020; 38(18): 2053-61.
[http://dx.doi.org/10.1200/JCO.19.03296] [PMID: 32343640]
[88]
Kloor M, Michel S, von Knebel Doeberitz M. Immune evasion of microsatellite unstable colorectal cancers. Int J Cancer 2010; 127(5): 1001-10.
[http://dx.doi.org/10.1002/ijc.25283] [PMID: 20198617]
[89]
Shin DS, Zaretsky JM, Escuin-Ordinas H, et al. Primary resistance to pd-1 blockade mediated by jak1/2 mutations. Cancer Discov 2017; 7(2): 188-201.
[http://dx.doi.org/10.1158/2159-8290.CD-16-1223] [PMID: 27903500]
[90]
Liu G-C, Liu R-Y, Yan J-P, et al. The heterogeneity between lynch-associated and sporadic mmr deficiency in colorectal cancers. J Natl Cancer Inst 2018; 110(9): 975-84.
[http://dx.doi.org/10.1093/jnci/djy004] [PMID: 29471527]
[91]
Sveen A, Johannessen B, Tengs T, et al. Multilevel genomics of colorectal cancers with microsatellite instability-clinical impact of JAK1 mutations and consensus molecular subtype 1. Genome Med 2017; 9(1): 46.
[http://dx.doi.org/10.1186/s13073-017-0434-0] [PMID: 28539123]
[92]
Binnewies M, Roberts EW, Kersten K, et al. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat Med 2018; 24(5): 541-50.
[http://dx.doi.org/10.1038/s41591-018-0014-x] [PMID: 29686425]
[93]
Chaput N, Lepage P, Coutzac C, et al. Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab. Ann Oncol 2017; 28(6): 1368-79.
[http://dx.doi.org/10.1093/annonc/mdx108] [PMID: 28368458]
[94]
Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets T V, et al. Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients. Science (80- ) 2018; 359(6371): 97-103.
[http://dx.doi.org/10.1126/science.aan4236]
[95]
Petrelli F, Iaculli A, Signorelli D, et al. Survival of patients treated with antibiotics and immunotherapy for cancer: a systematic review and meta-analysis. J Clin Med 2020; 9(5): 1458.
[http://dx.doi.org/10.3390/jcm9051458] [PMID: 32414103]
[96]
Koustas E, Sarantis P, Papavassiliou AG, Karamouzis MV. The resistance mechanisms of checkpoint inhibitors in solid tumors. Biomolecules 2020; 10(5): 666.
[http://dx.doi.org/10.3390/biom10050666] [PMID: 32344837]
[97]
Pérez-Ruiz E, Melero I, Kopecka J, et al. Cancer immunotherapy resistance based on immune checkpoints inhibitors: Targets, biomarkers, and remedies. Drug Resist Updat 2020; 53: 100718.
[http://dx.doi.org/10.1016/j.drup.2020.100718] [PMID: 32736034]
[98]
Sermer D, Brentjens R. CAR T-cell therapy: Full speed ahead. Hematol Oncol 2019; 37(S1)(Suppl. 1): 95-100.
[http://dx.doi.org/10.1002/hon.2591] [PMID: 31187533]
[99]
Sur D, Havasi A, Cainap C, et al. Chimeric antigen receptor t-cell therapy for colorectal cancer. J Clin Med 2020; 9(1): 182.
[http://dx.doi.org/10.3390/jcm9010182] [PMID: 31936611]
[100]
Lee DW, Gardner R, Porter DL, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood 2014; 124(2): 188-95.
[http://dx.doi.org/10.1182/blood-2014-05-552729] [PMID: 24876563]
[101]
Brudno JN, Kochenderfer JN. Recent advances in CAR T-cell toxicity: Mechanisms, manifestations and management. Blood Rev 2019; 34: 45-55.
[http://dx.doi.org/10.1016/j.blre.2018.11.002] [PMID: 30528964]
[102]
Neelapu SS. Managing the toxicities of CAR T-cell therapy. Hematol Oncol 2019; 37(S1)(Suppl. 1): 48-52.
[http://dx.doi.org/10.1002/hon.2595] [PMID: 31187535]
[103]
Hege KM, Bergsland EK, Fisher GA, et al. Safety, tumor trafficking and immunogenicity of chimeric antigen receptor (CAR)-T cells specific for TAG-72 in colorectal cancer. J Immunother Cancer 2017; 5(1): 22.
[http://dx.doi.org/10.1186/s40425-017-0222-9] [PMID: 28344808]
[104]
Sheen AJ, Irlam J, Kirillova N, et al. Gene therapy of patient-derived T lymphocytes to target and eradicate colorectal hepatic metastases. Dis Colon Rectum 2003; 46(6): 793-804.
[http://dx.doi.org/10.1007/s10350-004-6659-1] [PMID: 12794582]
[105]
Zhang C, Wang Z, Yang Z, et al. Phase i escalating-dose trial of car-t therapy targeting cea+ metastatic colorectal cancers. Mol Ther 2017; 25(5): 1248-58.
[http://dx.doi.org/10.1016/j.ymthe.2017.03.010] [PMID: 28366766]
[106]
Gao B. Natural killer group 2 member D, its ligands, and liver disease: good or bad? Hepatology 2010; 51(1): 8-11.
[http://dx.doi.org/10.1002/hep.23320] [PMID: 20034045]
[107]
Van Cutsem E, Machiels J, Van den Eynde M, Prenen H, Hendlisz A, Shaza L, et al. Phase 1 studies assessing the safety and clinical activity of autologous and allogeneic NKG2D-based CAR-T therapy in metastatic colorectal cancer. Ann Oncol 2019; 30: iv124-5.
[http://dx.doi.org/10.1093/annonc/mdz157.008]
[108]
Abdul-Latif M, Townsend K, Dearman C, Shiu K-K, Khan K. Immunotherapy in gastrointestinal cancer: The current scenario and future perspectives. Cancer Treat Rev 2020; 88: 102030.
[http://dx.doi.org/10.1016/j.ctrv.2020.102030] [PMID: 32505807]
[109]
Harris JE, Ryan L, Hoover HC Jr, et al. Adjuvant active specific immunotherapy for stage II and III colon cancer with an autologous tumor cell vaccine: Eastern Cooperative Oncology Group Study E5283. J Clin Oncol 2000; 18(1): 148-57.
[http://dx.doi.org/10.1200/JCO.2000.18.1.148] [PMID: 10623705]
[110]
Kawamura J, Sugiura F, Sukegawa Y, et al. Multicenter, phase II clinical trial of peptide vaccination with oral chemotherapy following curative resection for stage III colorectal cancer. Oncol Lett 2018; 15(4): 4241-7.
[PMID: 29541190]
[111]
Toubaji A, Achtar M, Provenzano M, et al. Pilot study of mutant ras peptide-based vaccine as an adjuvant treatment in pancreatic and colorectal cancers. Cancer Immunol Immunother 2008; 57(9): 1413-20.
[http://dx.doi.org/10.1007/s00262-008-0477-6] [PMID: 18297281]
[112]
Speetjens FM, Kuppen PJK, Welters MJP, et al. Induction of p53-specific immunity by a p53 synthetic long peptide vaccine in patients treated for metastatic colorectal cancer. Clin Cancer Res 2009; 15(3): 1086-95.
[http://dx.doi.org/10.1158/1078-0432.CCR-08-2227] [PMID: 19188184]
[113]
Rus Bakarurraini NAA, Ab Mutalib NS, Jamal R, Abu N. The landscape of tumor-specific antigens in colorectal cancer. Vaccines (Basel) 2020; 8(3): 371.
[http://dx.doi.org/10.3390/vaccines8030371] [PMID: 32664247]
[114]
Mandal R, Samstein RM, Lee K-W, Havel JJ, Wang H, Krishna C, et al. Genetic diversity of tumors with mismatch repair deficiency influences anti–PD-1 immunotherapy response. Science (80- ) 2019; 364(6439): 485-91.
[http://dx.doi.org/10.1126/science.aau0447]
[115]
Kopetz S, Andre T, Overman MJ, 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 + ipilimum. Clinical Research (Excluding Clinical Trials). American Association for Cancer Research 2018; 2603-3.
[http://dx.doi.org/10.1158/1538-7445.AM2018-2603]

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