Adaptive immune resistance is a process in which the cancer changes its phenotype in response to a cytotoxic or proinflammatory immune response, thereby evading it. This adaptive process is triggered by the specific recognition of cancer cells by T cells, which leads to the production of immune-activating cytokines. Cancers then hijack mechanisms developed to limit inflammatory and immune responses and protect themselves from the T-cell attack. Inhibiting adaptive immune resistance is the mechanistic basis of responses to PD-1 or PD-L1–blocking antibodies, and may be of relevance for the development of other cancer immunotherapy strategies.

Significance: Several new immunotherapy strategies to treat cancer are based on inhibiting processes through which cancer adapts and evades from an immune response. Recognizing the specific adaptive resistance mechanisms in each case is likely to allow the personalized development of immunotherapies tailored to block how a particular cancer protects itself from the immune system. Cancer Discov; 5(9); 915–9. ©2015 AACR.