Cancer Immunology at the Crossroads: Complementary Therapeutic Modalities Temperature Matters! And Why It Should Matter to Tumor Immunologists

A major goal of cancer immunotherapy is to stimulate the generation of long-lasting, tumor antigen–specific immune responses that recognize and destroy tumor cells. This article discusses advances in thermal medicine with the potential to improve cancer immunotherapy. Longstanding evidence indicates that survival benefits are accorded to individualswho achieve an increase in body temperature (i.e., fever) following infection. Furthermore, accumulating evidence indicates that physiologic responses to hyperthermia affect the tumormicroenvironment through temperature-sensitive checkpoints that regulate tumor vascular perfusion, lymphocyte trafficking, inflammatory cytokine expression, tumor metabolism, and innate and adaptive immune function. Nevertheless, the influence of thermal stimuli on the immune system, particularly the antitumor immune response, remains incompletely understood. In fact, temperature is still rarely considered as a critical variable in experimental immunology. We suggest that more attention should be directed to the role of temperature in the regulation of the immune response and that thermal therapy should be tested in conjunction with immunotherapy as a multi-functional adjuvant that modulates the dynamics of the tumor microenvironment. Cancer Immunol Res; 1(4); 210–6. 2013 AACR. Those who cannot be cured by medicine can be cured by surgery. Those who cannot be cured by surgery can be cured by heat. Those who cannot be cured by heat are to be considered incurable.