The hallmarks of cancer immune evasion

According to the widely accepted “three Es” model, the host immune system eliminates malignant cell precursors and contains microscopic neoplasms in a dynamic equilibrium, preventing cancer outgrowth until neoplastic cells acquire genetic or epigenetic alterations that enable immune escape. This immunoevasive phenotype originates from various mechanisms that can be classified under a novel “three Cs” conceptual framework: (1) camouflage, which hides cancer cells from immune recognition, (2) coercion, which directly or indirectly interferes with immune effector cells, and (3) cytoprotection, which shields malignant cells from immune cytotoxicity. Blocking the ability of neoplastic cells to evade the host immune system is crucial for increasing the efficacy of modern immunotherapy and conventional therapeutic strategies that ultimately activate anticancer immunosurveillance. Here, we review key hallmarks of cancer immune evasion under the “three Cs” framework and discuss promising strategies targeting such immunoevasive mechanisms.