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

Figure 2

Immune antigens expression by cancer cells contributes to the metastatic cascade. Most malignant solid tumors metastasize from the primary organ to another, such as the liver. At the primary site, potentially immunogenic tumor cells are being exposed to the immune system. High density of TILs and tumoricidal immune response mediated by killer cells and CD8+ T cells restrict the tumor outgrowth. Genetic damage and deregulated signaling pathways accompanied by the production of various cytokines and chemokines in the tumor microenvironment can induce expression of immune antigens on the cancer cell surface. By these changes, the tumors promote recruitment and expansion of prometastatic myeloid cells, TAMs, or TANs, respectively. As such, immune-like phenotype enables cancer cells to increase metastatic potential and avoid immune surveillance at different levels during the metastatic cascade. The circulating tumor cells expressing an immune-like phenotype, that is, CD47, are then arrested in microvessels in the metastatic site where they need to survive. At the metastatic site, the arrested tumor cells escape from the resident myeloid cells and survive at the metastatic niche and proliferate to form the deadly metastatic tumor. Recent studies suggest that MAMs sustain the survival and persistent growth of emigrated cancer cells. TANs also promote the entrapment of circulating cancer cells by producing neutrophil extracellular traps (NETs). TAMs: tumor associated macrophages; MAMs: metastasis-associated macrophages; TANs: tumor associated neutrophils.