Cancer patients mount adaptive immune responses against their tumor. However, while tumor-infiltrating lymphocytes and natural-killer (NK) cells try to detect and eliminate malignant cells, they eventually fail when these malignant cells develop mechanisms to evade effective immunosurveillance. First, malignant cells produce immunosuppressive cytokines and prostaglandins that skew the immune response toward a Th2 response, resulting in a humoral response with significantly less antitumor capacities, generating a low interleukin-2 environment blocking NK cell division, T-helper cell proliferation, and T-cytotoxic cell proliferation and function. Second, immunoresistant malignant cell variants emerge through selection of major histocompatibility class I and II and antigen-processing mutants reducing antigenicity. Finally, malignant cells may actively eliminate T-cells via activation-induced cell death or by mounting a counterattack through Fas ligand expression.