Immune Checkpoints as a Target for Colorectal Cancer Treatment

International Journal of Molecular Sciences - Tập 18 Số 6 - Trang 1324
Alessandro Passardi1, Matteo Canale2, Martina Valgiusti1, Paola Ulivi2
1Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy;
2Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy

Tóm tắt

Anti-tumor immunity is a new line of research for the treatment of patients with solid tumors. In this field, negative regulators of the immune system called immune checkpoints play a key role in limiting antitumor immunologic responses. For this reason, immune checkpoint-inhibiting agents, such as those directed against cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death-1 receptor (PD1) and its ligand PD-L1, have been developed as antitumor drugs, producing interesting results in preclinical and clinical studies. We present an updated review of the biological background and clinical development of immune checkpoint inhibitors in colorectal cancer (CRC). Early trial results on PD1 and PD-L1 blockade appear promising, especially in CRC patients with microsatellite instability (MSI). Clinical trials are ongoing to confirm these preliminary results, evaluate combination strategies and identify biomarkers to predict which patients are most likely to benefit from, or show resistance to, the effects of checkpoint inhibition.

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Tài liệu tham khảo

Bilgin, 2017, Targeting the PD-1 pathway: A new hope for gastrointestinal cancers, Curr. Med. Res. Opin., 33, 749, 10.1080/03007995.2017.1279132

Hanahan, 2011, Hallmarks of cancer: The next generation, Cell, 144, 646, 10.1016/j.cell.2011.02.013

Topalian, 2016, Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy, Nat. Rev. Cancer, 16, 275, 10.1038/nrc.2016.36

Pandya, 2016, The immune system in cancer pathogenesis: Potential therapeutic approaches, J. Immunol. Res., 2016, 4273943, 10.1155/2016/4273943

Schreiber, 2011, Cancer immunoediting: Integrating immunity’s roles in cancer suppression and promotion, Science, 331, 1565, 10.1126/science.1203486

Gubin, 2014, Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens, Nature, 515, 577, 10.1038/nature13988

Balkwill, 2001, Inflammation and cancer: Back to virchow?, Lancet, 357, 539, 10.1016/S0140-6736(00)04046-0

Mittal, 2014, New insights into cancer immunoediting and its three component phases—Elimination, equilibrium and escape, Curr. Opin. Immunol., 27, 16, 10.1016/j.coi.2014.01.004

Kyi, 2014, Checkpoint blocking antibodies in cancer immunotherapy, FEBS Lett., 588, 368, 10.1016/j.febslet.2013.10.015

Dunn, 2004, The three Es of cancer immunoediting, Annu. Rev. Immunol., 22, 329, 10.1146/annurev.immunol.22.012703.104803

Pardoll, 2012, The blockade of immune checkpoints in cancer immunotherapy, Nat. Rev. Cancer, 12, 252, 10.1038/nrc3239

Mahoney, 2015, Combination cancer immunotherapy and new immunomodulatory targets, Nat. Rev. Drug Discov., 14, 561, 10.1038/nrd4591

Das, 2017, Tim-3 and its role in regulating anti-tumor immunity, Immunol. Rev., 276, 97, 10.1111/imr.12520

Postow, 2015, Immune checkpoint blockade in cancer therapy, J. Clin. Oncol., 33, 1974, 10.1200/JCO.2014.59.4358

Shih, 2014, Clinical impact of checkpoint inhibitors as novel cancer therapies, Drugs, 74, 1993, 10.1007/s40265-014-0305-6

Naboush, 2017, Immune checkpoint inhibitors in malignancies with mismatch repair deficiency: A review of the state of the current knowledge, J. Investig. Med., 65, 754, 10.1136/jim-2016-000342

Krummel, 1996, CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression upon activation of resting T cells, J. Exp. Med., 183, 2533, 10.1084/jem.183.6.2533

Funt, 2014, CTLA-4 antibodies: New directions, new combinations, Oncology, 28, 6

Simpson, 2013, Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma, J. Exp. Med., 210, 1695, 10.1084/jem.20130579

Zou, 2008, Inhibitory B7-family molecules in the tumour microenvironment, Nat. Rev. Immunol., 8, 467, 10.1038/nri2326

Reiss, 2014, Harnessing the power of the immune system via blockade of PD-1 and PD-L1: A promising new anticancer strategy, Immunotherapy, 6, 459, 10.2217/imt.14.9

Kim, 2014, Prospects for targeting PD-1 and PD-L1 in various tumor types, Oncology, 28, 15

Taube, 2012, Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape, Sci. Transl. Med., 4, 127ra37, 10.1126/scitranslmed.3003689

Haggar, 2009, Colorectal cancer epidemiology: Incidence, mortality, survival, and risk factors, Clin. Colon Rectal Surg., 22, 191, 10.1055/s-0029-1242458

Jasperson, 2010, Hereditary and familial colon cancer, Gastroenterology, 138, 2044, 10.1053/j.gastro.2010.01.054

Lynch, 2003, Hereditary colorectal cancer, N. Engl. J. Med., 348, 919, 10.1056/NEJMra012242

Kastrinos, 2015, Comparison of prediction models for Lynch Syndrome among individuals with colorectal cancer, J. Natl. Cancer Inst., 108, djv308

Abdulovic, 2011, The in vitro fidelity of yeast DNA polymerase delta and polymerase epsilon holoenzymes during dinucleotide microsatellite DNA synthesis, DNA Repair, 10, 497, 10.1016/j.dnarep.2011.02.003

Hemminki, 1994, Loss of the wild type MLH1 gene is a feature of hereditary nonpolyposis colorectal cancer, Nat. Genet., 8, 405, 10.1038/ng1294-405

Popat, 2005, Systematic review of microsatellite instability and colorectal cancer prognosis, J. Clin. Oncol., 23, 609, 10.1200/JCO.2005.01.086

Samowitz, 2001, Microsatellite instability in sporadic colon cancer is associated with an improved prognosis at the population level, Cancer Epidemiol. Biomark. Prev., 10, 917

Veigl, 1998, Biallelic inactivation of hMLH1 by epigenetic gene silencing, a novel mechanism causing human MSI cancers, Proc. Natl. Acad. Sci. USA, 95, 8698, 10.1073/pnas.95.15.8698

Timmermann, B., Kerick, M., Roehr, C., Fischer, A., Isau, M., Boerno, S.T., Wunderlich, A., Barmeyer, C., Seemann, P., and Koenig, J. (2010). Somatic mutation profiles of MSI and MSS colorectal cancer identified by whole exome next generation sequencing and bioinformatics analysis. PLoS ONE, 5.

Schumacher, 2015, Neoantigens in cancer immunotherapy, Science, 348, 69, 10.1126/science.aaa4971

Galon, 2006, Type, density, and location of immune cells within human colorectal tumors predict clinical outcome, Science, 313, 1960, 10.1126/science.1129139

Quinn, 2003, CD103+ intraepithelial lymphocytes—A unique population in microsatellite unstable sporadic colorectal cancer, Eur. J. Cancer, 39, 469, 10.1016/S0959-8049(02)00633-0

Banerjea, 2004, Colorectal cancers with microsatellite instability display mRNA expression signatures characteristic of increased immunogenicity, Mol. Cancer, 3, 21, 10.1186/1476-4598-3-21

Phillips, 2004, Tumour-infiltrating lymphocytes in colorectal cancer with microsatellite instability are activated and cytotoxic, Br. J. Surg., 91, 469, 10.1002/bjs.4472

Saeterdal, 2001, Frameshift-mutation-derived peptides as tumor-specific antigens in inherited and spontaneous colorectal cancer, Proc. Natl. Acad. Sci. USA, 98, 13255, 10.1073/pnas.231326898

Domingo, 2016, Somatic POLE proofreading domain mutation, immune response, and prognosis in colorectal cancer: A retrospective, pooled biomarker study, Lancet Gastroenterol. Hepatol., 1, 207, 10.1016/S2468-1253(16)30014-0

Gatalica, 2014, Programmed cell death 1 (PD-1) and its ligand (PD-L1) in common cancers and their correlation with molecular cancer type, Cancer Epidemiol. Biomark. Prev., 23, 2965, 10.1158/1055-9965.EPI-14-0654

Llosa, 2015, The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints, Cancer Discov., 5, 43, 10.1158/2159-8290.CD-14-0863

Inaguma, 2017, Clinicopathologic profile, immunophenotype, and genotype of CD274 (PD-L1)-positive colorectal carcinomas, Mod. Pathol., 30, 278, 10.1038/modpathol.2016.185

Droeser, 2013, Clinical impact of programmed cell death ligand 1 expression in colorectal cancer, Eur. J. Cancer, 49, 2233, 10.1016/j.ejca.2013.02.015

Li, 2016, Prognostic impact of programed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) expression in cancer cells and tumor infiltrating lymphocytes in colorectal cancer, Mol. Cancer, 15, 55, 10.1186/s12943-016-0539-x

Alexandrov, 2013, Signatures of mutational processes in human cancer, Nature, 500, 415, 10.1038/nature12477

Chung, 2010, 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, 10.1200/JCO.2010.28.3994

Brahmer, 2010, 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, 10.1200/JCO.2009.26.7609

Topalian, 2012, Safety, activity, and immune correlates of anti-PD-1 antibody in cancer, N. Engl. J. Med., 366, 2443, 10.1056/NEJMoa1200690

Overman, 2017, Nivolumab in patients with DNA mismatch repair deficient/microsatellite instability high metastatic colorectal cancer: Update from CheckMate 142, J. Clin. Oncol., 35, 519, 10.1200/JCO.2017.35.4_suppl.519

Patnaik, 2015, Phase I study of pembrolizumab (MK-3475; Anti-PD-1 monoclonal antibody) in patients with advanced solid tumors, Clin. Cancer Res., 21, 4286, 10.1158/1078-0432.CCR-14-2607

Le, 2015, PD-1 blockade in tumors with mismatch-repair deficiency, N. Engl. J. Med., 372, 2509, 10.1056/NEJMoa1500596

Muro, 2016, Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): A multicentre, open-label, phase 1b trial, Lancet Oncol., 17, 717, 10.1016/S1470-2045(16)00175-3

Nanda, 2016, Pembrolizumab in patients with advanced triple-negative breast cancer: Phase Ib KEYNOTE-012 study, J. Clin. Oncol., 34, 2460, 10.1200/JCO.2015.64.8931

Plimack, 2017, Safety and activity of pembrolizumab in patients with locally advanced or metastatic urothelial cancer (KEYNOTE-012): A non-randomised, open-label, phase 1b study, Lancet Oncol., 18, 212, 10.1016/S1470-2045(17)30007-4

Diaz, 2017, Pembrolizumab therapy for microsatellite instability high (MSI-H) colorectal cancer (CRC) and non-CRC, J. Clin. Oncol., 35, 3071, 10.1200/JCO.2017.35.15_suppl.3071

Brahmer, 2012, Safety and activity of anti-PD-L1 antibody in patients with advanced cancer, N. Engl. J. Med., 366, 2455, 10.1056/NEJMoa1200694

Akbari, 2010, PD-L1 and PD-L2 modulate airway inflammation and iNKT-cell-dependent airway hyperreactivity in opposing directions, Mucosal Immunol., 3, 81, 10.1038/mi.2009.112

Matsumoto, 2008, B7-DC induced by IL-13 works as a feedback regulator in the effector phase of allergic asthma, Biochem. Biophys. Res. Commun., 365, 170, 10.1016/j.bbrc.2007.10.156

Bendell, 2015, Safety and efficacy of MPDL3280A (anti-PDL1) in combination with bevacizumab (bev) and/or FOLFOX in patients (pts) with metastatic colorectal cancer (mCRC), J. Clin. Oncol., 33, 704, 10.1200/jco.2015.33.3_suppl.704

Bendell, 2016, Clinical activity and safety of cobimetinib (Cobi) and atezolizumab in colorectal cancer (CRC), J. Clin. Oncol., 34, 3502, 10.1200/JCO.2016.34.15_suppl.3502