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ISSN (Print): 2212-697X
ISSN (Online): 2212-6988

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Review Article

Combining Chemotherapy with Immunotherapy in Colorectal Cancer: A Review

Author(s): John Thomas Palathingal*, Basil Sunny and Vismaya Vijayan

Volume 8, Issue 1, 2021

Published on: 29 October, 2020

Article ID: e301221187394 Pages: 8

DOI: 10.2174/2212697X07999201029200025

Price: $65

Abstract

American Cancer Society estimates that about 1 in 21 men and 1 in 23 women in US will develop colorectal cancer during their lifetime. Due to the advances in screening and treatment modalities, the mortality rate has reduced. Rising resistance to treatment has directed the focus towards different approaches as combination therapies involving different treatment techniques available. One such approach is chemo-immunotherapy that aims to modulate TIME and improve the response to immunotherapy. The chemo-immunotherapy has shown a positive impact on improving the outcome of CRC treatment. The ensemble of results discussed herein supports the role of biomarkers in determining the most effective treatment algorithm. Comprehensive knowledge about the off-target effects of the cytotoxic drugs helps in designing more efficacious combined treatment. The time-window for optimal combination must also be considered carefully.

Keywords: Combination therapy, colorectal cancer, chemo-immunotherapy, biomarkers, CRC treatment, cytotoxic drugs

Graphical Abstract

[1]
Hahn MM, de Voer RM, Hoogerbrugge N, Ligtenberg MJ, Kuiper RP, van Kessel AG. The genetic heterogeneity of colorectal cancer predisposition - guidelines for gene discovery. Cell Oncol (Dordr) 2016; 39(6): 491-510.
[http://dx.doi.org/10.1007/s13402-016-0284-6] [PMID: 27279102]
[2]
Nguyen HT, Duong HQ. The molecular characteristics of colorectal cancer: Implications for diagnosis and therapy. Oncol Lett 2018; 16(1): 9-18.
[http://dx.doi.org/10.3892/ol.2018.8679] [PMID: 29928381]
[3]
Colorectal Cancer. Conquer Cancer.The ASCO Foundation 2019.Https://Www.Cancer.Net/Cancer-Types/Colorectal-Cancer/View-All
[4]
Rawla P, Sunkara T, Barsouk A. Epidemiology of colorectal cancer: Incidence, mortality, survival, and risk factors. Gastroenterol Res 2019; 14(2): 89-103.
[http://dx.doi.org/10.5114/pg.2018.81072] [PMID: 31616522]
[5]
Millan M, Merino S, Caro A, Feliu F, Escuder J, Francesch T. Treatment of colorectal cancer in the elderly. World J Gastrointest Oncol 2015; 7(10): 204-20.
[http://dx.doi.org/10.4251/wjgo.v7.i10.204] [PMID: 26483875]
[6]
Get The Facts About Colon Cancer. Colon Cancer Coalition. Https://Coloncancercoalition.Org/Get-Educated /What-You-Need-To-Know/Colon-Cancer-Facts/
[7]
Sidaway P. Microenvironment plasticity confers cetuximab resistance. Nat Rev Clin Oncol 2019; 16(9): 527-7.
[http://dx.doi.org/10.1038/s41571-019-0259-4] [PMID: 31324873]
[8]
Fleming M, Ravula S, Tatishchev SF, Wang HL. Colorectal carcinoma: Pathologic aspects. J Gastrointest Oncol 2012; 3(3): 153-73.
[PMID: 22943008]
[9]
Colon Cancer Treatment(PDQ)-Healthcare Professional Version. National Cancer Institute Https://Www.Cancer.Gov/Types/Colorectal/Hp/Colon-Treatment-Pdq
[10]
Cancer Stat Facts: Colorectal Cancer. National Cancer Institute SEER Https://Seer.Cancer.Gov/Statfacts/Html/Colorectal.Html
[11]
Coverlizza S, Risio M, Ferrari A, Fenoglio-Preiser CM, Rossini FP. Colorectal adenomas containing invasive carcinoma. Pathologic assessment of lymph node metastatic potential. Cancer 1989; 64(9): 1937-47.
[http://dx.doi.org/10.1002/1097-0142(19891101)64:9<1937::AID-CNCR2820640929>3.0.CO;2-X] [PMID: 2477139]
[12]
Spallanzani A, Gelsomino F, Caputo F, et al. Immunotherapy in the treatment of colorectal cancer: A new kid on the block. J Cancer Metastasis Treat 2018; 4: 28.
[http://dx.doi.org/10.20517/2394-4722.2018.31]
[13]
Davis LE. The Evolution Of Biomarkers To Guide The Treatment Of Metastatic Colorectal Cancer. AJMC 2018.Https://Www.Ajmc.Com/Journals/Supplement/2018/Managing-Evolving-Landscape-Colorectal-Cancer/Evolution-Biomarkers-Guide-Treatment-Metastatic-Colorectal-Cancer
[14]
Mishra J, Dromund J, Quazi S H, et al. Prospective of colon cancer treatments and scope for combinatorial approach to enhanced cancer cell apoptosis. Crit Rev Oncol Hematol 2013; 86(3): 232-50.
[15]
Gang W, Wang JJ, Guan R, et al. Strategy to targeting the immune resistance and novel therapy in colorectal cancer. Cancer Med 2018; 7(5): 1578-603.
[http://dx.doi.org/10.1002/cam4.1386] [PMID: 29658188]
[16]
Markman JL, Shiao SL. Impact of the immune system and immunotherapy in colorectal cancer. J Gastrointest Oncol 2015; 6(2): 208-23.
[PMID: 25830040]
[17]
Swann JB, Smyth MJ. Immune surveillance of tumors. J Clin Invest 2007; 117(5): 1137-46.
[http://dx.doi.org/10.1172/JCI31405] [PMID: 17476343]
[18]
Lin CF, Lin CM, Lee KY, et al. Escape from INF-Γ-dependent immunosurveillance in tumorigenesis. J Biomed Sci 2017; 24(10): 1-9.
[19]
Atreya CE, Yaeger R, Chu E. Systemic Therapy for Metastatic Colorectal Cancer: From Current Standards to Future Molecular Targeted Approaches. Am Soc Clin Oncol Educ Book 2017; 37: 246-56.
[http://dx.doi.org/10.14694/EDBK_175679] [PMID: 28561718]
[20]
Henry JT, Johnson B. Current and evolving biomarkers for precision oncology in the management of metastatic colorectal cancer. Linchuang Zhongliuxue Zazhi 2019; 8(5): 49.
[http://dx.doi.org/10.21037/cco.2019.08.08] [PMID: 31500426]
[21]
Vogel A, Hofheinz RD, Kubicka S, Arnold D. Treatment decisions in metastatic colorectal cancer - Beyond first and second line combination therapies. Cancer Treat Rev 2017; 59: 54-60.
[http://dx.doi.org/10.1016/j.ctrv.2017.04.007] [PMID: 28738235]
[22]
Ciardiello D, Vitiello PP, Cardone C, et al. Immunotherapy of colorectal cancer: Challenges for therapeutic efficacy. Cancer Treat Rev 2019; 76: 22-32.
[http://dx.doi.org/10.1016/j.ctrv.2019.04.003] [PMID: 31079031]
[23]
Overman MJ, Ernstoff MS, Morse MA. Where we stand with immunotherapy in colorectal cancer: Deficient mismatch repair, proficient mismatch repair, and toxicity management. Am Soc Clin Oncol Educ Book 2018; 38: 239-47.
[http://dx.doi.org/10.1200/EDBK_200821] [PMID: 30231358]
[24]
Song W, Shen L, Wang Y, et al. Synergistic and low adverse effect cancer immunotherapy by immunogenic chemotherapy and locally expressed PD-L1 trap. Nat Commun 2018; 9(1): 2237.
[http://dx.doi.org/10.1038/s41467-018-04605-x] [PMID: 29884866]
[25]
Sensenbrenner LL, Owens AH Jr, Zawatzsky LS, Elfenbein GJ. Comparative effects of selected cytotoxic agents on transplanted hematopoietic cells. Transplantation 1972; 14(3): 347-51.
[http://dx.doi.org/10.1097/00007890-197209000-00010] [PMID: 4404694]
[26]
Boussios S, Pentheroudakis G, Katsanos K, Pavlidis N. Systemic treatment-induced gastrointestinal toxicity: Incidence, clinical presentation and management. Ann Gastroenterol 2012; 25(2): 106-18.
[PMID: 24713845]
[27]
Palathingal JT, Chalbatani GM, Rajan AK, et al. Case Report: Role Of Combination Therapy In Relapsed Ewing’s Sarcoma. Int J Biomed Sci 2019; 12(4): 112-6.
[28]
Nowak AK, Lake RA, Robinson BW. Combined chemoimmunotherapy of solid tumours: Improving vaccines? Adv Drug Deliv Rev 2006; 58(8): 975-90.
[http://dx.doi.org/10.1016/j.addr.2006.04.002] [PMID: 17005292]
[29]
Ménard C, Martin F, Apetoh L, Bouyer F, Ghiringhelli F. Cancer chemotherapy: Not only a direct cytotoxic effect, but also an adjuvant for antitumor immunity. Cancer Immunol Immunother 2008; 57(11): 1579-87.
[http://dx.doi.org/10.1007/s00262-008-0505-6] [PMID: 18369619]
[30]
Moschella F, Proietti E, Capone I, Belardelli F. Combination strategies for enhancing the efficacy of immunotherapy in cancer patients. Ann N Y Acad Sci 2010; 1194(1): 169-78.
[http://dx.doi.org/10.1111/j.1749-6632.2010.05464.x] [PMID: 20536466]
[31]
Zitvogel L, Apetoh L, Ghiringhelli F, Kroemer G. Immunological aspects of cancer chemotherapy. Nat Rev Immunol 2008; 8(1): 59-73.
[http://dx.doi.org/10.1038/nri2216] [PMID: 18097448]
[32]
Proietti E, Moschella F, Capone I, Belardelli F. Exploitation of the propulsive force of chemotherapy for improving the response to cancer immunotherapy. Mol Oncol 2012; 6(1): 1-14.
[http://dx.doi.org/10.1016/j.molonc.2011.11.005] [PMID: 22177803]
[33]
Botnick LE, Hannon EC, Vigneulle R, Hellman S. Differential effects of cytotoxic agents on hematopoietic progenitors. Cancer Res 1981; 41(6): 2338-42.
[PMID: 7237432]
[34]
Proietti E, Greco G, Garrone B, et al. Importance of cyclophosphamide-induced bystander effect on T cells for a successful tumor eradication in response to adoptive immunotherapy in mice. J Clin Invest 1998; 101(2): 429-41.
[http://dx.doi.org/10.1172/JCI1348] [PMID: 9435316]
[35]
Schlom J, Arlen PM, Gulley JL. Cancer vaccines: Moving beyond current paradigms. Clin Cancer Res 2007; 13(13): 3776-82.
[http://dx.doi.org/10.1158/1078-0432.CCR-07-0588] [PMID: 17606707]
[36]
Motoyoshi Y, Kaminoda K, Saitoh O, et al. Different mechanisms for anti-tumor effects of low- and high-dose cyclophosphamide. Oncol Rep 2006; 16(1): 141-6.
[http://dx.doi.org/10.3892/or.16.1.141] [PMID: 16786137]
[37]
Moschella F, Valentini M, Aricò E, et al. Unraveling cancer chemoimmunotherapy mechanisms by gene and protein expression profiling of responses to cyclophosphamide. Cancer Res 2011; 71(10): 3528-39.
[http://dx.doi.org/10.1158/0008-5472.CAN-10-4523] [PMID: 21444678]
[38]
Eberhard A, Kahlert S, Goede V, Hemmerlein B, Plate KH, Augustin HG. Heterogeneity of angiogenesis and blood vessel maturation in human tumors: Implications for antiangiogenic tumor therapies. Cancer Res 2000; 60(5): 1388-93.
[PMID: 10728704]
[39]
Miller KD, Sweeney CJ, Sledge GW Jr. Redefining the target: Chemotherapeutics as antiangiogenics. J Clin Oncol 2001; 19(4): 1195-206.
[http://dx.doi.org/10.1200/JCO.2001.19.4.1195] [PMID: 11181686]
[40]
Bertolini F, Paul S, Mancuso P, et al. Maximum tolerable dose and low-dose metronomic chemotherapy have opposite effects on the mobilization and viability of circulating endothelial progenitor cells. Cancer Res 2003; 63(15): 4342-6.
[PMID: 12907602]
[41]
Browder T, Butterfield CE, Kräling BM, et al. Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer. Cancer Res 2000; 60(7): 1878-86.
[PMID: 10766175]
[42]
Loeffler M, Krüger JA, Reisfeld RA. Immunostimulatory effects of low-dose cyclophosphamide are controlled by inducible nitric oxide synthase. Cancer Res 2005; 65(12): 5027-30.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-0646] [PMID: 15958544]
[43]
Atreya I, Neurath MF. Immune cells in colorectal cancer: Prognostic relevance and therapeutic strategies. Expert Rev Anticancer Ther 2008; 8(4): 561-72.
[http://dx.doi.org/10.1586/14737140.8.4.561] [PMID: 18402523]
[44]
Emens LA, Middleton G. The interplay of immunotherapy and chemotherapy: Harnessing potential synergies. Cancer Immunol Res 2015; 3(5): 436-43.
[http://dx.doi.org/10.1158/2326-6066.CIR-15-0064] [PMID: 25941355]
[45]
Lech G, Słotwiński R, Słodkowski M, Krasnodębski IW. Colorectal cancer tumour markers and biomarkers: Recent therapeutic advances. World J Gastroenterol 2016; 22(5): 1745-55.
[http://dx.doi.org/10.3748/wjg.v22.i5.1745] [PMID: 26855534]
[46]
Koido S, Ohkusa T, Homma S, et al. Immunotherapy for colorectal cancer. World J Gastroenterol 2013; 19(46): 8531-42.
[http://dx.doi.org/10.3748/wjg.v19.i46.8531] [PMID: 24379570]
[47]
Michaud M, Martins I, Sukkurwala AQ, et al. Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice. Science 2011; 334(6062): 1573-7.
[http://dx.doi.org/10.1126/science.1208347] [PMID: 22174255]
[48]
Inoue H, Tani K. Multimodal immunogenic cancer cell death as a consequence of anticancer cytotoxic treatments. Cell Death Differ 2014; 21(1): 39-49.
[http://dx.doi.org/10.1038/cdd.2013.84] [PMID: 23832118]
[49]
Hu X, Xuan Y. Bypassing cancer drug resistance by activating multiple death pathways--a proposal from the study of circumventing cancer drug resistance by induction of necroptosis. Cancer Lett 2008; 259(2): 127-37.
[http://dx.doi.org/10.1016/j.canlet.2007.11.007] [PMID: 18082322]
[50]
Bracci L, Schiavoni G, Sistigu A, Belardelli F. Immune-based mechanisms of cytotoxic chemotherapy: Implications for the design of novel and rationale-based combined treatments against cancer. Cell Death Differ 2014; 21(1): 15-25.
[http://dx.doi.org/10.1038/cdd.2013.67] [PMID: 23787994]
[51]
Weinberg F, Gadgeel S. Combination pembrolizumab plus chemotherapy: A new standard of care for patients with advanced non-small-cell lung cancer. Lung Cancer (Auckl) 2019; 10: 47-56.
[http://dx.doi.org/10.2147/LCTT.S176391] [PMID: 31239797]
[52]
Zhang Y, Xu J, Zhang N, Chen M, Wang H, Zhu D. Targeting the tumour immune microenvironment for cancer therapy in human gastrointestinal malignancies. Cancer Lett 2019; 458: 123-35.
[http://dx.doi.org/10.1016/j.canlet.2019.05.017] [PMID: 31121212]
[53]
Lesterhuis WJ, de Vries IJ, Aarntzen EA, et al. A pilot study on the immunogenicity of dendritic cell vaccination during adjuvant oxaliplatin/capecitabine chemotherapy in colon cancer patients. Br J Cancer 2010; 103(9): 1415-21.
[http://dx.doi.org/10.1038/sj.bjc.6605935] [PMID: 20924373]
[54]
Duan X, Chan C, Han W, Guo N, Weichselbaum RR, Lin W. Immunostimulatory nanomedicines synergize with checkpoint blockade immunotherapy to eradicate colorectal tumors. Nat Commun 2019; 10(1): 1899.
[http://dx.doi.org/10.1038/s41467-019-09221-x] [PMID: 31015397]
[55]
He C, Duan X, Guo N, et al. Core-shell nanoscale coordination polymers combine chemotherapy and photodynamic therapy to potentiate checkpoint blockade cancer immunotherapy. Nat Commun 2016; 7: 12499.
[http://dx.doi.org/10.1038/ncomms12499] [PMID: 27530650]
[56]
Wang ZX, Cao JX, Liu ZP, et al. Combination of chemotherapy and immunotherapy for colon cancer in China: A meta-analysis. World J Gastroenterol 2014; 20(4): 1095-106.
[http://dx.doi.org/10.3748/wjg.v20.i4.1095] [PMID: 24574784]
[57]
Ellebaek E, Andersen MH, Svane IM, Straten PT. Immunotherapy for metastatic colorectal cancer: Present status and new options. Scand J Gastroenterol 2012; 47(3): 315-24.
[http://dx.doi.org/10.3109/00365521.2012.640831] [PMID: 22214467]
[58]
Wada S, Yoshimura K, Hipkiss EL, et al. Cyclophosphamide augments antitumor immunity: Studies in an autochthonous prostate cancer model. Cancer Res 2009; 69(10): 4309-18.
[http://dx.doi.org/10.1158/0008-5472.CAN-08-4102] [PMID: 19435909]
[59]
Vanneman M, Dranoff G. Combining immunotherapy and targeted therapies in cancer treatment. Nat Rev Cancer 2012; 12(4): 237-51.
[http://dx.doi.org/10.1038/nrc3237] [PMID: 22437869]
[60]
Ghiringhelli F, Fumet J D. Is there a place for immunotherapy for metastatic microsatellite stable colorectal cancer? Frontiers In Immunology 1816; 10(1816): 1-10.
[61]
Rowe J, Cen P. TroVax in colorectal cancer. Hum Vaccin Immunother 2014; 10(11): 3196-200.
[http://dx.doi.org/10.4161/21645515.2014.973323] [PMID: 25483641]
[62]
Harrop R, Drury N, Shingler W, et al. Vaccination of colorectal cancer patients with modified vaccinia ankara encoding the tumor antigen 5T4 (TroVax) given alongside chemotherapy induces potent immune responses. Clin Cancer Res 2007; 13(15 Pt 1): 4487-94.
[http://dx.doi.org/10.1158/1078-0432.CCR-07-0704] [PMID: 17671134]
[63]
Kaufman HL, Lenz HJ, Marshall J, et al. Combination chemotherapy and ALVAC-CEA/B7.1 vaccine in patients with metastatic colorectal cancer. Clin Cancer Res 2008; 14(15): 4843-9.
[http://dx.doi.org/10.1158/1078-0432.CCR-08-0276] [PMID: 18676757]
[64]
Nowak AK, Robinson BWS, Lake RA. Synergy between chemotherapy and immunotherapy in the treatment of established murine solid tumors. Cancer Res 2003; 63(15): 4490-6.
[PMID: 12907622]
[65]
Fridlender ZG, Sun J, Singhal S, et al. Chemotherapy delivered after viral immunogene therapy augments antitumor efficacy via multiple immune-mediated mechanisms. Mol Ther 2010; 18(11): 1947-59.
[http://dx.doi.org/10.1038/mt.2010.159] [PMID: 20683443]
[66]
Botta C, Bestoso E, Apollinari S, et al. Immune-modulating effects of the newest cetuximab-based chemoimmunotherapy regimen in advanced colorectal cancer patients. J Immunother 2012; 35(5): 440-7.
[http://dx.doi.org/10.1097/CJI.0b013e31825943aa] [PMID: 22576349]
[67]
Apetoh L, Ladoire S, Coukos G, Ghiringhelli F. Combining immunotherapy and anticancer agents: The right path to achieve cancer cure? Ann Oncol 2015; 26(9): 1813-23.
[http://dx.doi.org/10.1093/annonc/mdv209] [PMID: 25922066]
[68]
Schiavoni G, Sistigu A, Valentini M, et al. Cyclophosphamide synergizes with type I interferons through systemic dendritic cell reactivation and induction of immunogenic tumor apoptosis. Cancer Res 2011; 71(3): 768-78.
[http://dx.doi.org/10.1158/0008-5472.CAN-10-2788] [PMID: 21156650]
[69]
Suzuki E, Kapoor V, Jassar AS, Kaiser LR, Albelda SM. Gemcitabine selectively eliminates splenic Gr-1+/CD11b+ myeloid suppressor cells in tumor-bearing animals and enhances antitumor immune activity. Clin Cancer Res 2005; 11(18): 6713-21.
[http://dx.doi.org/10.1158/1078-0432.CCR-05-0883] [PMID: 16166452]
[70]
Serafini P, De Santo C, Marigo I, et al. Derangement of immune responses by myeloid suppressor cells. Cancer Immunol Immunother 2004; 53(2): 64-72.
[http://dx.doi.org/10.1007/s00262-003-0443-2] [PMID: 14593498]
[71]
Kusmartsev S, Cheng F, Yu B, et al. All-trans-retinoic acid eliminates immature myeloid cells from tumor-bearing mice and improves the effect of vaccination. Cancer Res 2003; 63(15): 4441-9.
[PMID: 12907617]
[72]
Takimoto R, Kamigaki T, Okada S, et al. Prognostic Factors For Colorectal Cancer Patients Treated With Combination Of Immune-Cell Therapy And First-Line Chemotherapy: A Retrospective Study. 2019; 39(8): 4525-32.
[http://dx.doi.org/10.21873/anticanres.13629]

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