Colorectal cancer and immunity: What we know and perspectives

Abstract

Strong evidence supports the concept of immunosurveillance and immunoediting in colorectal cancer. In particular, the density of T CD8⁺ and CD45⁺ lymphocyte infiltration was recently shown to have a better prognostic value than the classic tumor node metastasis classification factor. Other immune subsets, as macrophages, natural killer cells or unconventionnal lymphocytes, seem to play an important role. Induction of regulatory T cells (Tregs) or immunosuppressive molecules such as PD-1 or CTLA-4 and downregulation of antigen-presenting molecules are major escape mechanisms to antitumor immune response. The development of these mechanisms is a major obstacle to the establishment of an effective immune response, but also to the use of immunotherapy. Although immunotherapy is not yet routinely used in colorectal cancer, we now know that most treatments used (chemotherapy and biotherapy) have immunomodulatory effects, such as induction of immunogenic cell death by chemotherapy, inhibition of immunosuppression by antiangiogenic agents, and antibody-dependent cytotoxicity induced by cetuximab. Finally, many immunotherapy strategies are being developed and tested in phase I to III clinical trials. The most promising strategies are boosting the immune system with cytokines, inhibition of immunoregulatory checkpoints, vaccination with vectorized antigens, and adoptive cell therapy. Comprehension of antitumor immune response and combination of the different approaches of immunotherapy may allow the use of effective immunotherapy for treatment of colorectal cancer in the near future.

Keywords: Colorectal cancer, Immunotherapy, Immunity, Immunoregulation, Vaccination

Core tip: Immune system is now widely accepted as a key mechanism to prevent occurrence of cancer and intratumoral T CD8⁺ and CD45⁺ lymphocytes infiltrate has shown to be a major prognosis factor in colorectal cancer. However, immunity fail in controlling tumor growth, because of strong escape mechanisms to the immune system developed by the tumor. In recent years, several immunotherapy strategies have been tested in colorectal cancer. This review provides an understanding of the mechanisms involved and identifies innovating therapeutic strategies.