Immunotherapeutic Approaches for the Treatment of Colorectal Cancer

Abstract

Colorectal cancer (CRC) originating from the cells of the colon or rectum has a high mortality rate worldwide. Numerous attempts have been made to raise the overall survival rates of CRC patients. It is well-known that the development of malignant neoplasms is accompanied by suppression of the immune system, which is likely the cause for the failure of standard treatment methods. Immune response has long been an issue of great interest in cancer therapy and anti-tumor immunity that consider the development of immunotherapeutic antitumor methods resulting in the immune system activation as an important issue. This review discusses main immunotherapeutic approaches available for the CRC treatment.

Abbreviations

ACT:

adoptive cell immunotherapy

CAR T cell:

T cell with chimeric antigen receptor

CEA:

carcinoembryonic antigen

CRC:

colorectal cancer

DC:

dendritic cell

ICPI:

immune checkpoint inhibitor

TCR:

high-avidity T-cell receptor

TIL:

tumor-infiltrating lymphocyte

References

  1. 1.

    World Health Organization, International Agency for Research on Cancer. GLOBOCAN 2012: Estimated cancer incidence, mortality, and prevalence worldwide in 2012. Cancer fact sheets (http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx), Accessed June 5, 2018.

    Google Scholar 

  2. 2.

    Kaprin, A. D., Starinskii, V. V., and Petrova, G. V. (eds.) (2017) Occurrence of Cancer in Russia in 2017: Morbidity and Mortality [in Russian], Gertsen Moscow Research Oncology Institute, Moscow.

    Google Scholar 

  3. 3.

    Raskov, H., Pommergaard, H. C., Burcharth, J., and Rosenberg, J. (2014) Colorectal carcinogenesis-update and perspectives, World J. Gastroenterol., 20, 18151–18164; doi: 10.3748/wjg.v20.i48.18151.

    Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Wang, Q., and Wu, X. (2017) Primary and acquired resistance to PD-1/PD-L1 blockade in cancer treatment, Int. Immunopharmacol., 46, 210–219; doi: 10.1016/j.intimp. 2017.03.015.

    Article  CAS  PubMed  Google Scholar 

  5. 5.

    Nowicki, T. S., Hu-Lieskovan, S., and Ribas, A. (2018) Mechanisms of resistance to PD-1 and PD-L1 blockade, Cancer J., 24, 47–53; doi: 10.1097/PPO.0000000000000303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Seow, H. F., Yip, W. K., and Fifis, T. (2016) Advances in targeted and immunobased therapies for colorectal cancer in the genomic era, OncoTargets Ther., 9, 1899–1920; doi: 10.2147/OTT.S95101.

    Article  CAS  Google Scholar 

  7. 7.

    Grothey, A., Flick, E. D., Cohn, A. L., Bekaii-Saab, T. S., Bendell, J. C., Kozloff, M., Roach, N., Mun, Y., Fish, S., and Hurwitz Bevacizumab, H. I. (2014) Exposure beyond first disease progression in patients with metastatic colorec-tal cancer: analyses of the ARIES observational cohort study, Pharmacoepidemiol. Drug Saf., 23, 726–734; doi: 10.1002/pds.3633.

    Article  CAS  PubMed  Google Scholar 

  8. 8.

    Marmol, I., Sanchez-de-Diego, C., Pradilla Dieste, A., Cerrada, E., and Rodriguez Yoldi, M. J. (2017) Colorectal carcinoma: a general overview and future perspectives in colorectal cancer, Int. J. Mol. Sci., 18, 197; doi: 10.3390/ijms18010197.

    Google Scholar 

  9. 9.

    Rezaeeyan, H., Hassani, S. N., Barati, M., Shahjahani, M., and Saki, N. (2017) PD-1/PD-L1 as a prognostic factor in leukemia, J. Hematopathol., 10, 17–24; doi: 10.1007/s12308-017-0293-z.

    Article  Google Scholar 

  10. 10.

    Gianchecchi, E., Delfino, D. V., and Fierabracci, A. (2013) Recent insights into the role of the PD-1/PD-L1 pathway in immunological tolerance and autoimmunity, Autoimmun. Rev., 12, 1091–1100; doi: 10.1016/j.autrev. 2013.05.003.

    Article  CAS  PubMed  Google Scholar 

  11. 11.

    Kamphorst, A. O., Wieland, A., Nasti, T., Yang, S., Zhang, R., Barber, D. L., Konieczny, B. T., Daugherty, C. Z., Koenig, L., Yu, K., Sica, G. L., Sharpe, A. H., Freeman, G. J., Blazar, B. R., Turka, L. A., Owonikoko, T. K., Pillai, R. N., Ramalingam, S. S., Araki, K., and Ahmed, R. (2017) Rescue of exhausted CD8 T cells by PD-1-targeted therapies is CD28-dependent, Science, 355, 1423–1427; doi: 10.1126/science.aaf0683.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Hoos, A., Ibrahim, R., Korman, A., Abdallah, K., Berman, D., Shahabi, V., Chin, K., Canetta, R., and Humphrey, R. (2010) Development of ipilimumab: contribution to a new paradigm for cancer immunotherapy, Semin. Oncol., 37, 533–546; doi: 10.1053/j.seminoncol.2010.09.015.

    Article  CAS  PubMed  Google Scholar 

  13. 13.

    Pardoll, D. M. (2012) The blockade of immune checkpoints in cancer immunotherapy, Nat. Rev. Cancer, 12, 252–264; doi: 10.1038/nrc3239.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Xu-Monette, Z. Y., Zhang, M., Li, J., and Young, K. H. (2017) PD-1/PD-L1 blockade: have we found the key to unleash the antitumor immune response? Front. Immunol., 8, 1597; doi: 10.3389/fimmu.2017.01597.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Volkov, N. M. (2018) Immunotherapy, Pract. Oncol., 19, 226–235; doi: 10.31917/1903226.

    Article  Google Scholar 

  16. 16.

    Yaghoubi, N., Soltani, A., Ghazvini, K., Hassanian, S. M., and Hashemy, S. I. (2019) PD-1/PD-L1 blockade as a novel treatment for colorectal cancer, Biomed. Pharmacother., 110, 312–318; doi: 10.1016/j.biopha.2018. 11.105.

    Article  CAS  PubMed  Google Scholar 

  17. 17.

    Brahmer, J. R., Drake, C. G., Wollner, I., Powderly, J. D., Picus, J., Sharfman, W. H., Stankevich, E., Pons, A., Salay, T. M., McMiller, T. L., Gilson, M. M., Wang, C., Selby, M., Taube, J. M., Anders, R., Chen, L., Korman, A. J., Pardoll, D. M., Lowy, I., and Topalian, S. L. (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, 3167–3175; doi: 10.1200/JCO.2009.26.7609.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Overman, M. J., McDermott, R., Leach, J. L., Lonardi, S., Lenz, H. J., Morse, M. A., Desai, J., Hill, A., Axelson, M., and Moss, R. A. (2017) Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatel-lite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study, Lancet Oncol., 18, 1182–1191; doi: 10.1016/S1470-2045(17)30422-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. 19.

    O’Neil, B. H., Wallmark, J. M., Lorente, D., Elez, E., Raimbourg, J., Gomez-Roca, C., Ejadi, S., Piha-Paul, S. A., Stein, M. N., and Abdul Razak, R. A. (2017) Safety and antitumor activity of the anti-PD-1 antibody pem-brolizumab in patients with advanced colorectal carcinoma, PLoS One, 12, e0189848; doi: 10.1371/journal.pone. 0189848.

    Google Scholar 

  20. 20.

    Brahmer, J. R., Tykodi, S. S., Chow, L. Q., Hwu, W. J., Topalian, S. L., Hwu, P., Drake, C. G., Camacho, L. H., Kauh, J., and Odunsi, K. (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer, N. Engl. J. Med., 366, 2455–2465; doi: 10.1056/NEJMoa1200694.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Zhong, X., Tumang, J. R., Gao, W., Bai, C., and Rothstein, T. L. (2007) PD-L2 expression extends beyond dendritic cells/macrophages to B1 cells enriched for V(H)11/V(H)12 and phosphatidylcholine binding, Eur. J. Immunol., 37, 2405–2410; doi: 10.1002/eji.200737461.

    Article  CAS  PubMed  Google Scholar 

  22. 22.

    Wang, H., Yao, H., Li, C., Liang, L., Zhang, Y., Shi, H., Zhou, C., Chen, Y., Fang, J. Y., and Xu, J. (2017) PD-L2 expression in colorectal cancer: independent prognostic effect and targetability by deglycosylation, Oncoimmunology, 6, 7; doi: 10.1080/2162402X.2017. 1327494.

    Google Scholar 

  23. 23.

    Arora, S. P., and Mahalingam, D. (2018) Immunotherapy in colorectal cancer: for the select few or all, J. Gastrointest. Oncol., 9, 170–179; doi: 10.21037/jgo.2017.06.10.

    Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Seledtsova, G. V., Shishkov, A. A., Kaschenko, E. A., and Seledtsov, V. I. (2016) Xenogeneic cell-based vaccine therapy for colorectal cancer: safety, association of clinical effects with vaccine-induced immune responses, Biomed. Pharmacother., 83, 1247–1252; doi: 10.1016/j.biopha. 2016.08.050.

    Article  CAS  PubMed  Google Scholar 

  25. 25.

    Bilusic, M., Heery, C. R., Arlen, P. M., Rauckhorst, M., Apelian, D., Tsang, K. Y., Tucker, J. A., Jochems, C., Schlom, J., Gulley, J. L., and Madan, R. A. (2014) Phase I trial of a recombinant yeast-CEA vaccine (GI-6207) in adults with metastatic CEA-expressing carcinoma, Cancer Immunol. Immunother., 63, 225–234; doi: 10.1007/s00262-013-1505-8.

    Article  CAS  PubMed  Google Scholar 

  26. 26.

    Markov, O. V., Mironova, N. L., Vlasov, V. V., and Zenkova, M. A. (2017) Anti-tumor vaccines based on dendritic cells: from animal model experiments to clinical trials, Acta Naturae, 9, 29–41.

    Article  Google Scholar 

  27. 27.

    Lesterhuis, W. J., De Vries, I. J., Schreibelt, G., Schuurhuis, D. H., Aarntzen, E. H., De Boer, A., Scharenborg, N. M., Van De Rakt, M., Hesselink, E. J., Figdor, C. G., Adema, G. J., and Punt, C. J. (2010) Immunogenicity of dendritic cells pulsed with CEA peptide or transfected with CEA mRNA for vaccination of colorec-tal cancer patients, Anticancer Res., 30, 5091–5097.

    PubMed  Google Scholar 

  28. 28.

    Zhou, X., Mo, X., Qiu, J., Zhao, J., Wang, S., Zhou, C., Su, Y., Lin, Z., and Ma, H. (2018) Chemotherapy combined with dendritic cell vaccine and cytokine-induced killer cells in the treatment of colorectal carcinoma: a meta-analysis, Cancer Manag. Res., 10; doi: 10.2147/CMAR.S173201.

    Google Scholar 

  29. 29.

    Fan, J., Shang, D., Han, B., Song, J., Chen, H., and Yang, J. M. (2018) Adoptive cell transfer: is it a promising immunotherapy for colorectal cancer, Theranostics, 8; doi: 10.7150/thno.29035.

    Google Scholar 

  30. 30.

    Abakushina, E. V., and Kozlov, I. G. (2016) Immunotherapy with the natural killer cells in the treatment of cancer, Rus. J. Immunol., 10, 131–142 (Russ.).

    Google Scholar 

  31. 31.

    Borobova, E. A., and Zheravin, A. A. (2018) Natural killer cells in immunotherapy for cancer, Siberian J. Oncol., 17, 97–104; doi: 10.21294/1814-4861-2018-17-6-97-104.

    Article  Google Scholar 

  32. 32.

    Zhen, Y. H., Liu, X. H., Yang, Y., Li, B., Tang, J. L., Zeng, Q. X., Hu, J., Zeng, X. N., Zhang, L., Wang, Z. J., Li, X. Y., Ge, H. X., Winqvist, O., Hu, P. S., and Xiu, J. (2015) Phase I/II study of adjuvant immunotherapy with sentinel lymph node T lymphocytes in patients with colorectal cancer, Cancer Immunol. Immunother., 64, 1083–1093; doi: 10.1007/s00262-015-1715-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Parkhurst, M. R., Yang, J. C., Langan, R. C., Dudley, M. E., Nathan, D. A., Feldman, S. A., Davis, J. L., Morgan, R. A., Merino, M. J., Sherry, R. M., Hughes, M. S., Kammula, U. S., Phan, G. Q., Lim, R. M., Wank, S. A., Restifo, N. P., Robbins, P. F., Laurencot, C. M., and Rosenberg, S. A. (2011) T cells targeting carcinoembryon-ic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis, Mol. Ther., 19, 620–626; doi: 10.1038/mt. 2010.272.

    Article  CAS  PubMed  Google Scholar 

  34. 34.

    Morgan, R. A., Yang, J. C., Kitano, M., Dudley, M. E., Laurencot, C. M., and Rosenberg, S. A. (2010) Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2, Mol. Ther., 18, 843–851; doi: 10.1038/mt.2010.24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Zhang, L., Mu, Y., Zhang, A., Xie, J., Chen, S., Xu, F., Wang, W., Zhang, Y., Ren, S., and Zhou, C. (2017) Cytokine-induced killer cells/dendritic cells-cytokine induced killer cells immunotherapy combined with chemotherapy for treatment of colorectal cancer in China: a meta-analysis of 29 trials involving 2610 patients, Oncotarget, 8, 45164–45177; doi: 10.18632/oncotarget.16665.

    PubMed  PubMed Central  Google Scholar 

  36. 36.

    Kaleta-Richter, M., Kawczyk-Krupka, A., Aebisher, D., Bartusik-Aebisher, D., Czuba, Z., and Cieslar, G. (2019) The capabilities and hope of the combination the new forms of personalized colon cancer treatment - immunotherapy and immune photodynamic therapy, Photodiagn. Photodyn. Ther., 25, 253–258; doi: 10.1016/j.pdpdt.2019.01.004.

    Article  Google Scholar 

  37. 37.

    Anokhin, Yu. N., and Abakushina, E. V. (2016) Tumor-specific immune-response after photodynamic therapy, Med. Immunol. (Russia), 18, 405–416 (In Russ.); doi: 10.15789/1563-0625-2016-5-405-416.

    Article  Google Scholar 

  38. 38.

    Yoshida, Y., Naito, M., Yamada, T., Aisu, N., Kojima, D., Mera, T., Tanaka, T., Naito, K., Yasumoto, K., Kamigaki, T., Gotoh, S., Kodama, S., Yamashita, Y., and Hasegawa, S. (2017) Clinical study on medical value of adoptive immunotherapy with chemotherapy for stage IV colorectal cancer (COMVI study), Anticancer Res., 37, 3941–3946; doi: 10.21873/anticanres.11777.

    CAS  PubMed  Google Scholar 

  39. 39.

    Abakushina, E. V., Pasova, I. A., Pochuev, T. P., Evdokimov, L. V., Berdov, B. A., and Kaprin, A. D. (2017) Adoptive immunotherapy with activated lymphocytes in complex therapy of colon cancer patients, Ros. Bioterapevt. Zh., 16, S1.

    Google Scholar 

  40. 40.

    Reichman, H., Itan, M., Rozenberg, P., Yarmolovski, T., Brazowski, E., Varol, C., Gluck, N., Shapira, S., Arber, N., Qimron, U., Karo-Atar, D., Lee, J. J., and Munitz, A. (2019) Activated eosinophils exert antitumorigenic activities in colorectal cancer, Cancer Immunol. Res., 7, 388–400; doi: 10.1158/2326-6066.CIR-18-0494.

    Article  PubMed  Google Scholar 

  41. 41.

    Fritz, J., Karakhanova, S., Brecht, R., Schwaab, K., Nachtigall, I., Werner, J., and Bazhin, A. V. (2015) In vitro immunomodulatory properties of gemcitabine alone and in combination with interferon-alpha, Immunol. Lett., 168, 111–119; doi: 10.1016/j.imlet.2015.09.017.

    Article  CAS  PubMed  Google Scholar 

  42. 42.

    Yang, J. L., Qu, X. J., Russell, P. J., and Goldstein, D. (2005) Interferon-alpha promotes the anti-proliferative effect of gefitinib (ZD 1839) on human colon cancer cell lines, Oncology, 69, 224–238; doi: 10.1159/000088070.

    Article  CAS  PubMed  Google Scholar 

  43. 43.

    Kit, O. I., Maksimov, A. Y., Novikova, I. A., Grankina, A. O., Zlatnik, E. Y., Kirichenko, E. Y., and Filippova, S. Y. (2017) Colorectal cancer immunotherapy: current state and prospects (review), CTM, 9, 138–148; doi: 10.17691/stm2017.9.3.18.

    Google Scholar 

  44. 44.

    Correale, P., Botta, C., Rotundo, M. S., Guglielmo, A., Conca, R., Licchetta, A., Pastina, P., Bestoso, E., Ciliberto, D., Cusi, M. G., Fioravanti, A., Guidelli, G. M., Bianco, M. T., Misso, G., Martino, E., Caraglia, M., Tassone, P., Mini, E., Mantovani, G., Ridolfi, R., Pirtoli, L., and Tagliaferri, P. (2014) Gemcitabine, oxaliplatin, lev-ofolinate, 5-fluorouracil, granulocyte-macrophage colony-stimulating factor, and interleukin-2 (GOLFIG) versus FOLFOX chemotherapy in metastatic colorectal cancer patients: the GOLFIG-2 multicentric open-label randomized phase III trial, Immunotherapy, 37, 26–35; doi: 10.1097/CJI.0000000000000004.

    Article  CAS  Google Scholar 

  45. 45.

    Goloshchapov, R. S., Kokov, L. S., Vishnevskiy, V. A., Ionkin, D. A., and Elagina, L. V. (2003) Regional arterial chemoembolization and chemoimmunoembolization in complex treatment of colon cancer with liver metastases, Khirurgiya, 7, 66–71.

    Google Scholar 

  46. 46.

    Yu, P., Steel, J. C., Zhang, M., Morris, J. C., and Waldmann, T. A. (2010) Simultaneous blockade of multiple immune inhibitory checkpoints enhance anti-tumor activity mediated by interleukin-15 in a murine metastatic colon carcinoma model, Clin. Cancer Res., 16, 6019–6028; doi: 10.1158/1078-0432.CCR-10-1966.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. 47.

    Horn, L. A., Long, T. M., Atkinson, R. V., Clements, V., and Ostrand-Rosenberg, S. (2018) Soluble CD80 protein delays tumor growth and promotes tumor-infiltrating lymphocytes, Cancer Immunol. Res., 6, 59–68; doi: 10.1158/2326-6066.CIR-17-0026.

    Article  CAS  PubMed  Google Scholar 

  48. 48.

    Netesov, S. V., Kochneva, G. V., Loktev, V. B., Svyatchenko, V. A., Sergeev, A. N., Ternovoi, V. A., Tikunova, N. V., Shishkina, L. N., and Chumakov, P. M. (2011) Oncolytic viruses: advances and problems, Med. Alfavit, 3, 26–33.

    Google Scholar 

  49. 49.

    Geevarghese, S. K., Geller, D. A., de Haan, H. A., Horer, M., Knoll, A. E., Mescheder, A., Nemunaitis, J., Reid, T. R., Sze, D. Y., Tanabe, K. K., and Tawfik, H. (2010) Phase I/II study of oncolytic herpes simplex virus NV1020 in patients with extensively pretreated refractory colorectal cancer metastatic to the liver, Hum. Gene Ther., 21, 1119–1128; doi: 10.1089/hum.2010.020.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. 50.

    Manservigi, R., Argnani, R., and Marconi, P. (2010) HSV recombinant vectors for gene therapy, Open Virol. J., 4, 123–156; doi: 10.2174/1874357901004010123.

    CAS  Google Scholar 

  51. 51.

    Woller, N., Gurlevik, E., Fleischmann-Mundt, B., Schumacher, A., Knocke, S., Kloos, A. M., Saborowski, M., Geffers, R., Manns, M. P., Wirth, T. C., Kubicka, S., and Kuhnel, F. (2015) Viral infection of tumors overcomes resistance to PD-1-immunotherapy by broadening neoantigenome-directed T-cell responses, Mol. Ther., 23, 1630–1640; doi: 10.1038/mt.2015.115.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. 52.

    Sharma, K. K., Kalyani, I. H., Mohapatra, J., Patel, S. D., Patel, D. R., Vihol, P. D., Chatterjee, A., Patel, D. R., and Vyas, B. (2017) Evaluation of the oncolytic potential of R2B Mukteshwar vaccine strain of Newcastle disease virus (NDV) in a colon cancer cell line (SW-620), Arch. Virol., 162, 2705–2713; doi: 10.1007/s00705-017-3411-4.

    Article  CAS  PubMed  Google Scholar 

  53. 53.

    Rusch, T., Bayry, J., Werner, J., Shechenko, I., and Bazhin, A. V. (2018) Immunotherapy as an option for cancer treatment, Arch. Immunol. Ther. Exp., 66, 89–96; doi: 10.1007/s00005-017-0491-5.

    Article  CAS  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to E. V. Abakushina.

Additional information

Russian Text © The Author(s), 2019, published in Biokhimiya, 2019, Vol. 84, No. 7, pp. 923–933.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Abakushina, E.V., Gelm, Y.V., Pasova, I.A. et al. Immunotherapeutic Approaches for the Treatment of Colorectal Cancer. Biochemistry Moscow 84, 720–728 (2019). https://doi.org/10.1134/S0006297919070046

Download citation

Keywords

  • colorectal cancer (CRC)
  • immunotherapy
  • checkpoint inhibition
  • programmed death 1 (PD-1)
  • adoptive cell immunotherapy