Topic Highlight
Copyright ©2014 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Apr 14, 2014; 20(14): 3738-3750
Published online Apr 14, 2014. doi: 10.3748/wjg.v20.i14.3738
Colorectal cancer and immunity: What we know and perspectives
Simon Pernot, Magali Terme, Thibault Voron, Orianne Colussi, Elie Marcheteau, Eric Tartour, Julien Taieb
Simon Pernot, Orianne Colussi, Julien Taieb, Service d’Hépatogastro-entérologie et d’oncologie digestive, Hôpital Européen Georges-Pompidou, Université Paris Descartes, Sorbonne Paris Cité, 75015 Paris, France
Magali Terme, Thibault Voron, Elie Marcheteau, Eric Tartour, Julien Taieb, INSERM U970, Paris Cardiovascular Research Center, Université Paris-Descartes, 75006 Paris, France
Eric Tartour, Service d’Immunologie biologique, Hôpital Européen Georges-Pompidou, Université Paris Descartes, Sorbonne Paris Cité, 75015 Paris, France
Author contributions: Pernot S and Terme M wrote the paper; Pernot S, Terme M, Voron T, Colussi O, Marcheteau E, Tartour E and Taieb J helped conduct the literature review, analyze and discuss the litterature review and implications and commented on the manuscript at all stages.
Correspondence to: Dr. Julien Taieb, Service d’Hépatogastro-entérologie et d’oncologie digestive, Hôpital Européen Georges-Pompidou, Université Paris Descartes, Sorbonne Paris Cité 20, rue Leblanc, 75015 Paris, France. julien.taieb@egp.aphp.fr
Telephone: +33-1-56095042 Fax: +33-1-53987952
Received: October 31, 2013
Revised: January 8, 2014
Accepted: January 20, 2014
Published online: April 14, 2014
Processing time: 165 Days and 4 Hours
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.