Cancer-Associated Immune Resistance and Evasion of Immune Surveillance in Colorectal Cancer

Figure 1

Tumor microenvironment and subversion of immunosurveillance during carcinogenesis. At early stage of primary tumor expansion, the immune system can specifically identify and eliminate tumor cells on the basis of their expression of specific antigens “highly immunogenic tumor.” However, there might not be a complete elimination leading to the survival of some cancer cells that nevertheless remain under immunosurveillance “state of equilibrium.” If the immune response fails to completely eliminate the tumor, cancer cells can avoid or suppress the antitumor immune response leading to a progressively growing tumor. In the case of colorectal cancer (CRC) subtypes, different combinations of genetic and epigenetic changes lead to well distinct microsatellite stable (MMRp) or unstable or MMRd subtypes with different mutational load. Studies have shown that MMRd CRC have a high number of somatic mutations, “hypermutated tumors,” that can give rise to neoepitopes or damage-associated molecular patterns (DAMPs) and that these may serve as neoantigens for activation of tumor-specific CD8 T cell responses. The large majority of CRC are nonhypermutated cases tending to exhibit chromosomal instability associated with loss of tumor antigens, loss of human leukocyte antigen molecules, loss of sensitivity to complement, or T cell lysis, making them a poor target of an immune attack.