Standard therapies: solutions for improving therapeutic effects of immune checkpoint inhibitors on colorectal cancer

References

• Allemani C, Matsuda T, Di Carlo V, Harewood R, Matz M, Nikšić M, Bonaventure A, Valkov M, Johnson CJ, Estève J, et al. Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet. 2018;391:1023–9. doi:10.1016/S0140-6736(17)33326-3.
   PubMed Web of Science ®Google Scholar
• 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. 2018;36:773–779. doi:10.1200/JCO.2017.76.9901.
   PubMed Web of Science ®Google Scholar
• Emambux S, Tachon G, Junca A, Tougeron D. Results and challenges of immune checkpoint inhibitors in colorectal cancer. Expert Opin Biol Ther. 2018;18:561–573. doi:10.1080/14712598.2018.1445222.
   PubMed Web of Science ®Google Scholar
• Sanmamed MF, Chen L. A paradigm shift in cancer immunotherapy: from enhancement to normalization. Cell. 2018;175:313–326. doi:10.1016/j.cell.2018.09.035.
   PubMed Web of Science ®Google Scholar
• Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D, Aranda Aguilar E, Bardelli A, Benson A, Bodoky G, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016;27(8):1386–1422. doi:10.1093/annonc/mdw235.
   PubMed Web of Science ®Google Scholar
• Glynne-Jones R, Wyrwicz L, Tiret E, Brown G, Rödel C, Cervantes A, Arnold D, ESMO Guidelines Committee. Rectal cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2017;28:iv22–iv40. doi:10.1093/annonc/mdx224.
   PubMed Web of Science ®Google Scholar
• Fukumura D, Klopper J, Amoozgar Z, Duda DG, Jain RK. Enhancing cancer immunotherapy using antiantiogenics: opportunities and challenges. Nat Rev Clin Oncol. 2018;15:325–340. doi:10.1038/nrclinonc.2018.29.
   PubMed Web of Science ®Google Scholar
• Brooks ED, Chang JY. Time to abandon single-site irradiation for inducing abscopal effects. Nat Rev Clin Oncol. 2018;16:123–135. doi:10.1038/s41571-018-0119-7.
   Web of Science ®Google Scholar
• Gong J, Le TQ, Massarelli E, Hendifar AE, Tuli R. Radiation therapy and PD-1/PD-L1 blockade: the clinical development of an evolving anticancer combination. J Immunother Cancer. 2018;6:46. doi:10.1186/s40425-018-0361-7.
   PubMed Web of Science ®Google Scholar
• Galon J, Pagès F, Marincola FM, Angell HK, Thurin M, Lugli A, Zlobec I, Berger A, Bifulco C, Botti G, et al. Cancer classification using the immunoscore: a worldwide task force. J Transl Med. 2012;10:205. doi:10.1186/1479-5876-10-205.
   PubMed Web of Science ®Google Scholar
• Guinney J, Dienstmann R, Wang X, de Reyniès A, Schlicker A, Soneson C, Marisa L, Roepman P, Nyamundanda G, Angelino P, et al. The consensus molecular subtypes of colorectal cancer. Nat Med. 2015;21:1350–1356. doi:10.1038/nm.3967.
   PubMed Web of Science ®Google Scholar
• Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513:202–209. doi:10.1038/nature13480.
   PubMed Web of Science ®Google Scholar
• Cancer Genome Atlas Research Network. Comprehensive genomic characterization of squamous cell lung cancers. Nature. 2012;489:519–525. doi:10.1038/nature11404.
   PubMed Web of Science ®Google Scholar
• Rudin CM, Poirier JT, Byers LA, Dive C, Dowlati A, George J, Heymach JV, Johnson JE, Lehman JM, MacPherson D, et al. Molecular subtypes of small cell lung cancers: a synthesis of human and mouse model data. Nat Rev Cancer. 2019;19:289–297. doi:10.1038/s41568-019-0133-9.
   PubMed Web of Science ®Google Scholar
• Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018;359:1350–1355. doi:10.1126/science.aar4060.
   PubMed Web of Science ®Google Scholar
• van der Merwe PA, Davis SJ. Molecular interaction mediating T cell antigen recognition. Annu Rev Immunol. 2003;21:659–684. doi:10.1146/annurev.immunol.21.120601.141036.
   PubMed Web of Science ®Google Scholar
• Lee KM, Chuang E, Griffin M, Khattri R, Hong DK, Zhang W, Straus D, Samelson LE, Thompson CB, Bluestone JA, et al. Molecular basis of T cell inactivation by CTLA-4. Science. 1998;282:2263–2266. doi:10.1126/science.282.5397.2263.
   PubMed Web of Science ®Google Scholar
• McLane LM, Abdel-Hakeem MS, Wherry EJ. CD8 T cell exhaustion during chronic viral infection and cancer. Annu Rev Immunol. 2019;37:457–495. doi:10.1146/annurev-immunol-041015-055318.
   PubMed Web of Science ®Google Scholar
• Chen G, Huang AC, Zhang W, Zhang G, Wu M, Xu W, Yu Z, Yang J, Wang B, Sun H, et al. Exosomal PD-L1 contributes to immune suppression and is associated with anti-PD-1 response. Nature. 2018;560:382–386. doi:10.1038/s41586-018-0392-8.
   PubMed Web of Science ®Google Scholar
• Huang AC, Postow MA, Orlowski RJ, Mick R, Bengsch B, Manne S, Xu W, Harmon S, Giles JR, Wenz B, et al. T-cell invigoration to tumour burden ratio associated with anti-PD-1 response. Nature. 2017;545(7652):60–65. doi:10.1038/nature22079.
   PubMed Web of Science ®Google Scholar
• Guo X, Zhang Y, Zheng L, Zheng C, Song J, Zhang Q, Kang B, Liu Z, Jin L, Xing R, et al. Global characterization of T cells in non-small-cell lung cancer by single-cell sequencing. Nat Med. 2018;24(7):978–985. doi:10.1038/s41591-018-0045-3.
   PubMed Web of Science ®Google Scholar
• Yost KE, Satpathy AT, Wells DK, Qi Y, Wang C, Kageyama R, McNamara KL, Granja JM, Sarin KY, Brown RA, et al. Clonal replacement of tumor-specific T cells following PD-1 blockade. Nat Med. 2019;25(8):1251–1259. doi:10.1038/s41591-019-0522-3.
   PubMed Web of Science ®Google Scholar
• Theelen WSME, Peulen HMU, Lalezari F, van der Noort V, de Vries JF, Aerts JGJV, Dumoulin DW, Bahce I, Niemeijer ALN, de Langen AJ, et al. Effect of Pembrolizumab After stereotactic Body radiotherapy vs Pembrolizumab alone on tumor response in patients with advanced non-small cell lung cancer: results of the PEMBRO-RT phase 2 randomized clinical trial. JAMA Oncol. Eput 2019 Jul 11;5(9):1276. doi:10.1001/jamaoncol.2019.1478
   PubMed Web of Science ®Google Scholar
• Barclay AN, Van den Berg TK. The interaction between signal regulatory protein alpha (SIRPα) and CD47: structure, function, and therapeutic target. Annu Rev Immunol. 2014;32:25–50. doi:10.1146/annurev-immunol-032713-120142.
   PubMed Web of Science ®Google Scholar
• Joyce JA, Fearon DT. T cell exclusion, immune privilege, and the tumor microenvironment. Science. 2015;348:74–80. doi:10.1126/science.aaa6204.
   PubMed Web of Science ®Google Scholar
• Garrido-Ramos MA. Satellite DNA: an evolving topic. Genes. 2017;8:230. doi:10.3390/genes8090230.
   PubMed Web of Science ®Google Scholar
• Boland PM, Yurgelun MB, Boland CR. Recent progress in Lynch syndrome and other familial colorectal cancer syndromes. CA Cancer J Clin. 2018;68:217–231. doi:10.3322/caac.21448.
   PubMed Web of Science ®Google Scholar
• Dienstmann R, Vermeulen L, Guinney J, Kopetz S, Tejpar S, Tabernero J. Consensus molecular subtypes and the evolution of precision medicine in colorectal cancer. Nat Rev Cancer. 2017;17:79–92. doi:10.1038/nrc.2017.24.
   PubMed Web of Science ®Google Scholar
• Grasso CS, Giannakis M, Wells DK, Hamada T, Mu XJ, Quist M, Nowak JA, Nishihara R, Qian ZR, Inamura K, et al. Genetic mechanisms of immune evasion in colorectal cancer. Cancer Discov. 2018;8:730–749. doi:10.1158/2159-8290.CD-17-1327.
   PubMed Web of Science ®Google Scholar
• Broussard EK, Disis ML. TNM staging in colorectal cancer: T is for T cell and M is for memory. J Clin Oncol. 2011;29:601–603. doi:10.1200/JCO.2010.32.9078.
   PubMed Web of Science ®Google Scholar
• O’Neil BH, Funkhouser WK, Calvo BF, Meyers MO, Kim HJ, Goldberg RM, Bernard SA, Caskey L, Deal AM, Wright F, et al. Nuclear factor κ-light chain-enhancer of activated B cells is activated by radiotherapy and is prognostic for overall survival in patients with rectal cancer treated with preoperative fluorouracil-based chemoradiotherapy. Int J Radiat Oncol Biol Phys. 2011;80(3):705–711. doi:10.1016/j.ijrobp.2010.02.063.
   PubMed Web of Science ®Google Scholar
• Leonard W, Dufait I, Schwarze JK, Law K, Engels B, Jiang H, Van den Berge D, Gevaert T, Storme G, Verovski V, et al. Myeloid-derived suppressor cells reveal radioprotective properties through arginase-induced I-arginine depletion. Radiother Oncol. 2016;119:291–299. doi:10.1016/j.radonc.2016.01.014.
   PubMed Web of Science ®Google Scholar
• Saigusa S, Toiyama Y, Tanaka K, Yokoe T, Okugawa Y, Kawamoto A, Yasuda H, Inoue Y, Miki C, Kusunoki M, et al. Stromal CXCR4 and CXCL12 expression is associated with distant recurrence and poor prognosis in rectal cancer after chemoradiotherapy. Ann Surg Oncol. 2010;17:2051–2058. doi:10.1245/s10434-010-0970-y.
   PubMed Web of Science ®Google Scholar
• D’Alterio C, Avallone A, Tatangelo F, Delrio P, Pecori B, Cella L, Pelella A, D’Armiento FP, Carlomagno C, Bianco F, et al. A prognostic model comprising pT stage, N status, and the chemokine receptors CXCR4 and CXCR7 powerfully predicts outcome in neoadjuvant resistant rectal cancer patients. Int J Cancer. 2014;135:379–390. doi:10.1002/ijc.28689.
   PubMed Web of Science ®Google Scholar
• Samarendra H, Jones K, Petrinic T, Silva MA, Reddy S, Soonawalla Z, Gordon-Weeks A. A meta-analysis of CXCL12 expression for cancer prognosis. Br J Cancer. 2017;117:124–135. doi:10.1038/bjc.2017.134.
   PubMed Web of Science ®Google Scholar
• Heylmann D, Rödel F, Kindler T, Kaina B. Radiation sensitivity of human and murine peripheral blood lymphocytes, stem and progenitor cells. Biochim Biophys Acta. 2014;1846:121–129. doi:10.1016/j.bbcan.2014.04.009.
   PubMed Web of Science ®Google Scholar
• Kim TD, Li G, Song KS, Kim JM, Kim JS, Yun EJ, Park JI, Park HD, Hwang BD, Lim K, et al. Radiation-induced thymidine phosphorylase upregulation in rectal cancer is mediated by tumor-associated macrophages by monocyte chemoattactant protein-1 from cancer cells. Int J Radiat Oncol Biol Phys. 2009;73:853–860. doi:10.1016/j.ijrobp.2008.07.068.
   PubMed Web of Science ®Google Scholar
• Itatani Y, Kawada K, Inamoto S, Yamamoto T, Ogawa R, Taketo MM, Sakai Y. The role of chemokines in promoting colorectal cancer invasion/metastasis. Int J Mol Sci. 2016;17:pii: E643. doi:10.3390/ijms17050643.
   PubMed Web of Science ®Google Scholar
• Barker HE, Paget JT, Khan AA, Harrington KJ. The tumor microenvironment after radiotherapy: mechanisms of resistance and recurrence. Nat Rev Cancer. 2015;15:409–425. doi:10.1038/nrc3958.
   PubMed Web of Science ®Google Scholar
• Kroemer G, Galluzzi L, Kepp O, Zitvogel L. Immunogenic cell death in cancer therapy. Annu Rev Immunol. 2013;31:51–72. doi:10.1146/annurev-immunol-032712-100008.
   PubMed Web of Science ®Google Scholar
• Schollbach J, Kircher S, Wiegering A, Seyfried F, Klein I, Rosenwald A, Germer C-T, Löb S. Prognostic value of tumour-infiltrating CD8+ lymphocytes in rectal cancer after neoadjuvant chemoradiation: is indoleamine-2,3-dioxygenase (IDO1) a friend or foe? Cancer Immunol Immunother. 2019;68:563–575. doi:10.1007/s00262-019-02306-y.
   PubMed Web of Science ®Google Scholar
• Matsutani S, Shibutani M, Maeda K, Nagahara H, Fukuoka T, Nakao S, Hirakawa K, Ohira M. Significance of tumor-infiltrating lymphocytes before and after neoadjuvant therapy for rectal cancer. Cancer Sci. 2018;109:966–979. doi:10.1111/cas.13542.
   PubMed Web of Science ®Google Scholar
• Shinto E, Hase K, Hashiguchi Y, Sekizawa A, Ueno H, Shikina A, Kajiwara Y, Kobayashi H, Ishiguro M, Yamamoto J, et al. CD8+ and FOXP3+ tumor-infiltrating T cells before and after chemoradiaotherapy for rectal cancer. Ann Surg Oncol. 2014;21(Suppl 3):S414–21. doi:10.1245/s10434-014-3584-y.
   PubMed Web of Science ®Google Scholar
• Yasuda K, Nirei T, Sunami E, Nagawa H, Kitayama J. Density of CD4(+) and CD8(+) T lymphocytes in biopsy samples can be a predictor of pathological response to chemoradiotherapy (CRT) for rectal cancer. Radiat Oncol. 2011;6:49. doi:10.1186/1748-717X-6-49.
   PubMed Web of Science ®Google Scholar
• Teng F, Meng X, Kong L, Mu D, Zhu H, Liu S, Zhang J, Yu J. TILs, FOXP3, PD-L1 and CTLA-4 expressions before and after neoadjuvant chemoradiation in rectal cancer. Transl Res. 2015;166:721–732.e1. doi:10.1016/j.trsl.2015.06.019.
   PubMed Web of Science ®Google Scholar
• Anitei MG, Zeitoun G, Mlecnik B, Marliot F, Haicheur N, Todosi AM, Kirilovsky A, Lagorce C, Bindea G, Ferariu D, et al. Prognostic and predictive values of the immunoscore in patients with rectal cancer. Clin Cancer Res. 2014;20:1891–1899. doi:10.1158/1078-0432.CCR-13-2830.
   PubMed Web of Science ®Google Scholar
• Carducci MA, Giblin J, Dottellis D. 2019 ASCO annual meeting proceedings. J Clin Oncol. 2019;37:192s.
   Google Scholar
• Garcia-Aguilar J, Chow OS, Smith DD, Marcet JE, Cataldo PA, Varma MG, Kumar AS, Oommen S, Coutsoftides T, Hunt SR, et al. Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicenter, phase 2 trial. Lancet Oncol. 2015;16:957–966. doi:10.1016/S1470-2045(15)00004-2.
   PubMed Web of Science ®Google Scholar
• Chiang SF, Huang CY, Ke TW, Chen TW, Lan YC, You YS, Chen WT, Chao KSC. Upregulation of tumor PD-L1 by neoadjuvant chemoradiotherapy (neoCRT) confers imporved survival in patients with lymph node metastasis of locally advanced rectal cancers. Cancer Immunol Immunother. 2019;68:283–296. doi:10.1007/s00262-018-2275-0.
   PubMed Web of Science ®Google Scholar
• Ogura A, Akiyoshi T, Yamamoto N, Kawachi H, Ishikawa Y, Mori S, Oba K, Nagino M, Fukunaga Y, Ueno M, et al. Pattern of programmed death-ligand 1 expression and CD8-positive T-cell infiltration before and after chemoradiotherapy in rectal cancer. Eur J Cancer. 2018;91:11–20. doi:10.1016/j.ejca.2017.12.005.
   PubMed Web of Science ®Google Scholar
• Fuks Z, Kolesnick R. Engaging the vascular component of the tumor response. Cancer Cell. 2005;8:89–91. doi:10.1016/j.ccr.2005.07.014.
   PubMed Web of Science ®Google Scholar
• Song CW, Kim MS, Cho LC, Dusenbery K, Sperduto PW. Radiobiological basis of SBRT and SRS. Int J Clin Oncol. 2014;19:570–578. doi:10.1007/s10147-014-0717-z.
   PubMed Web of Science ®Google Scholar
• Deloch L, Derer A, Hartmann J, Frey B, Fietkau R, Gaipl US. Modern radiotherapy concepts and the impact of radiation on immune activation. Front Oncol. 2016;6:141. doi:10.3389/fonc.2016.00141.
   PubMed Web of Science ®Google Scholar
• Baumann M, Krause M, Hill R. Exploring the roles of cancer stem cells in radioresistance. Nat Rev Cancer. 2018;8:545–554. doi:10.1038/nrc2419.
   Web of Science ®Google Scholar
• Prager BC, Xie Q, Bao S, Rich JN. Cancer stem cells: the architects of the tumor ecosystem. Cell Stem Cell. 2019;24:41–53. doi:10.1016/j.stem.2018.12.009.
   PubMed Web of Science ®Google Scholar
• Popp I, Grosu AL, Niedermann G, Duda DG. Immune modulation by hypofractionated stereotactic radiation therapy: therapeutic implications. Radiother Oncol. 2016;120:185–194. doi:10.1016/j.radonc.2016.07.013.
   PubMed Web of Science ®Google Scholar
• Hellevik T, Martinez-Zubiaurre I. Radiotherapy and the tumor stroma: the importance of dose and fractionation. Front Oncol. 2014;4:1. doi:10.3389/fonc.2014.00001.
   PubMedGoogle Scholar
• Arnold KM, Flynn NJ, Raben A, Romak L, Yu Y, Dicker AP, Mourtada F, Sims-Mourtada J. The impact of radiation on the tumor microenviroment: effect of dose and fractionation schedules. Cancer Growth Metastasis. 2018;11:1179064418761639. doi:10.1177/1179064418761639.
   Web of Science ®Google Scholar
• Luke JJ, Lemons JM, Karrison TG, Pitroda SP, Melotek JM, Zha Y, Al-Hallaq HA, Arina A, Khodarev NN, Janisch L, et al. Safety and clinical activity of Pembrolizumab and multisite stereotactic body radiotherapy in patients with advanced solid tumors. J Clin Oncol. 2018;36(16):1611–1618. doi:10.1200/JCO.2017.76.2229.
   PubMed Web of Science ®Google Scholar
• Li J, Yuan Y, Yang F, Wang Y, Zhu X, Wang Z, Zheng S, Wan D, He J, Wang J, et al. Expert consensus on multidisciplinary therapy of colorectal cancer with lung metastases (2019 edition). J Hematol Oncol. 2019;12(1):16. doi:10.1186/s13045-019-0702-0.
   PubMed Web of Science ®Google Scholar
• Tesniere A, Schlemmer F, Boige V, Kepp O, Martins I, Ghiringhelli F, Aymeric L, Michaud M, Apetoh L, Barault L, et al. Immunogenic death of colon cancer cells treated with oxaliplatin. Oncogene. 2010;29(4):482–491. doi:10.1038/onc.2009.356.
   PubMed Web of Science ®Google Scholar
• Duffy AG, Greten TF. Immunological off-target effects of standard treatments in gastrointestinal cancer. Ann Oncol. 2014;25:24–32. doi:10.1093/annonc/mdt349.
   PubMed Web of Science ®Google Scholar
• Kalanxhi E, Meltzer S, Schou JV, Larsen FO, Dueland S, Flatmark K, Jensen BV, Hole KH, Seierstad T, Redalen KR, et al. Systemic immune response induced by oxaliplatin-based neoadjuvant therapy favors survival without metastatic progression in high-risk rectal cancer. Br J Cancer. 2018;118(10):1322–1328. doi:10.1038/s41416-018-0085-y.
   PubMed Web of Science ®Google Scholar
• Song W, Shen L, Wang Y, Liu Q, Goodwin TJ, Li J, Dorosheva O, Liu T, Liu R, Huang L, et al. Synergistic and low adverse effect cancer immunotherapy by immunogenic chemotherapy and locally expressed PD-L1 trap. Nat Commun. 2018;9(1):2237. doi:10.1038/s41467-018-04605-x.
   PubMed Web of Science ®Google Scholar
• Melichar B, Touskova M, Vesely P. Effect of irinotecan on the phenotype of peripheral blood leukocyte populations in patients with metastatic colorectal cancer. Hepatogastroenterology. 2002;49:967–970.
   PubMedGoogle Scholar
• Maeda K, Hazama S, Tokuno K, Kan S, Meada Y, Watanabe Y, Kamei R, Shindo Y, Maeda N, Yoshimura K, et al. Impact of chemotherapy for colorectal cancer on regulatory T-cells and tumor immunity. Anticancer Res. 2011;31:4569–4574.
   PubMed Web of Science ®Google Scholar
• Fumet JD, Isambert N, Hervieu A, Zanetta S, Guion JF, Hennequin A, Rederstorff E, Bertaut A, Ghiringhelli F. Phase Ib/II trail evaluating the safety, tolerability and immunological activity of durvalumab (MEDI4736) (anti-PD-L1) plus Tremelimumab (anti-CTLA-4) combined with FOLFOX in patients with metastatic colorectal cancer. ESMO Open. 2018;3:e000375. doi:10.1136/esmoopen-2018-000375.
   PubMed Web of Science ®Google Scholar
• Serna-Blasco R, Sanz-Álvarez M, Aguilera Ó, García-Foncillas J. Targeting the RAS-dependent chemoresistance: the Warburg connection. Semin Cancer Biol. 2019;54:80–90. doi:10.1016/j.semcancer.2018.01.016.
   PubMed Web of Science ®Google Scholar
• 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 multicenter, open-label, phase 3, randomized, controlled trial. Lancet Oncol. 2019;20:849–861. doi:10.1016/S1470-2045(19)30027-0.
   PubMed Web of Science ®Google Scholar
• Botrel TEA, Clark LGO, Paladini L, Clark OAC. Efficacy and safety of bevacizumab plus chemotherapy compared to chemotherapy alone in previously untreated advanced or metastatic colorectal cancer: a systematic review and meta-analysis. BMC Cancer. 2016;16:677. doi:10.1186/s12885-016-2734-y.
   PubMed Web of Science ®Google Scholar
• D’Alterio C, Nasti G, Polimeno M, Ottaiano A, Conson M, Circelli L, Botti G, Scognamiglio G, Santagata S, De Divitiis C, et al. CXCR4-CXCL12-CXCR7 TLR2-TLR4, and PD-1/PD-L1 in colorectal cancer liver metastases from neoadjuvant-treated patients. Oncoimmunology. 2016;5:e1254313. doi:10.1080/2162402X.2016.1254313.
   PubMed Web of Science ®Google Scholar
• 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. 2016;76:5241–5252. doi:10.1158/0008-5472.CAN-15-3164.
   PubMed Web of Science ®Google Scholar
• Palazon A, Tyrakis PA, Macias D, Velica P, Rundqvist H, Fitzpatrick S, Vojnovic N, Phan AT, Loman N, Hedenfalk I, et al. An HIF-1α/VEGF-A axis in cytotoxic t cells regulates tumor progression. Cancer Cell. 2017;32(5):669–683.e5. doi:10.1016/j.ccell.2017.10.003.
   PubMed Web of Science ®Google Scholar
• Van den Eynde M, Mlecnik B, Bindea G, Fredriksen T, Church SE, Lafontaine L, Haicheur N, Marliot F, Angelova M, Vasaturo A, et al. The Link between the multiverse of immune microenviroments in metastases and the survival of colorectal cancer patients. Cancer Cell. 2018;34:1012–1026.e3. doi:10.1016/j.ccell.2018.11.003.
   PubMed Web of Science ®Google Scholar
• Luo W, He WT, Wen Q, Chen S, Wu J, Chen XP, Ma L. Changes of TCR repertoire diversity in colorectal cancer after erbitux (cetuximab) in combination with chemotherapy. Am J Cancer Res. 2014;4:924–933.
   PubMed Web of Science ®Google Scholar
• Correale P, Botta C, Cusi MG, Del Vecchio MT, De Santi MM, Gori Savellini G, Bestoso E, Apollinari S, Mannucci S, Marra M, et al. Cetuximab ± chemotherapy enhances dendritic cell-mediated phagocytosis of colon cancer cells and ignites a highly efficient colon cancer antigen-specific cytotoxic T-cell response in vitro. Int J Cancer. 2012;130(7):1577–1589. doi:10.1002/ijc.26181.
   PubMed Web of Science ®Google Scholar
• Jobin G, Rodriguez-Suarez R, Betito K. Association between natural killer cell activity and colorectal cancer in high-risk subjects undergoing colonoscopy. Gastroenterology. 2017;153:980–987. doi:10.1053/j.gastro.2017.06.009.
   PubMed Web of Science ®Google Scholar
• Seo H, Jeon I, Kim BS, Park M, Bae EA, Song B, Koh CH, Shin KS, Kim IK, Choi K, et al. IL-21-mediated reversal of NK cell exhaustion facilitates anti-tumour immunity in MHC class I-deficient tumours. Nat Commun. 2017;8:15776. doi:10.1038/ncomms15776.
   PubMed Web of Science ®Google Scholar
• Steele N, Anthony A, Saunders M, Esmarck B, Ehrnrooth E, Kristjansen PE, Nihlén A, Hansen LT, Cassidy J. A phase 1 trial of recombinant human IL-21 in combination with cetuximab in patients with metastatic colorectal cancer. Br J Cancer. 2012;106:793–798. doi:10.1038/bjc.2011.599.
   PubMed Web of Science ®Google Scholar
• Ishikawa T, Okayama T, Sakamoto N, Ideno M, Oka K, Enoki T, Mineno J, Yoshida N, Katada K, Kamada K, et al. Phase I clinical trial of adoptive transfer of expanded natural killer cells in combination with IgG1 antibody in patient with gastric or colorectal cancer. Int J Cancer. 2018;142:2599–2609. doi:10.1002/ijc.31285.
   PubMed Web of Science ®Google Scholar
• Kohrt HE, Colevas AD, Houot R, Weiskopf K, Goldstein MJ, Lund P, Mueller A, Sagiv-Barfi I, Marabelle A, Lira R, et al. Targeting CD137 enhances the efficacy of cetuximab. J Clin Invest. 2014;124(6):2668–2682. doi:10.1172/JCI73014.
   PubMed Web of Science ®Google Scholar
• Russo M, Crisafulli G, Sogari A, Reilly NM, Arena S, Lamba S, Bartolini A, Amodio V, Magrì A, Novara L, et al. Adaptive mutability of colorectal cancers in response to targeted therapies. Science. 2019;366(6472):1473–1480. doi:10.1126/science.aav4474.
   PubMed Web of Science ®Google Scholar