Immune microenvironment in colorectal cancer: a new hallmark to change old paradigms

Abstract

Impact of immune microenvironment in prognosis of solid tumors has been extensively studied in the last few years. Specifically in colorectal carcinoma, increased knowledge of the immune events around these tumors and their relation with clinical outcomes have led to consider immune microenvironment as one of the most important prognostic factors in this disease. In this review we will summarize and update the current knowledge with respect to this intriguing and complex new hallmark of cancer, paying special attention to infiltration by T-infiltrating lymphocytes and their subtypes in colorectal cancer, as well as its eventual clinical translation in terms of long-term prognosis. Finally, we suggest some possible investigational approaches based on combinatorial strategies to trigger and boost immune reaction against tumor cells.

Figure 1

(1) CTLA-4 is a negative regulator of T-cell activation. (2) Conventional T-cells are activated by engagement of MHC and B7. (3) Upon activation, T-cells express CTLA-4 on the cells surface and the union of CTLA-4 with B7 inhibits T-cell activation. (4) Antibody blockade of CTLA-4 produces the liberation of CD28 which could engage with B7 with the best activation of T-cells.

Figure 2

Early Apoptotic Phase: Calreticulin (CRT). oxaliplatin induces translocation of the intracytoplasmic protein calreticulin to the cell surface, inducing the apoptotic cell antigen presentation to dendritic cells and stimulating specific antitumor T-cell responses.