Temperature matters! And why it should matter to tumor immunologists - PubMed (original) (raw)

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Temperature matters! And why it should matter to tumor immunologists

Elizabeth A Repasky et al. Cancer Immunol Res. 2013 Oct.

Abstract

A major goal of cancer immunology 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. Accumulating evidence indicates that survival benefits are accorded to individuals who achieve an increase in body temperature (i.e. fever) following infection. Furthermore, accumulating evidence indicates that physiological responses to hyperthermia impact the tumor microenvironment through temperature-sensitive check-points 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 antitum or 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.

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Figure 1

Figure 1

A multi-functional adjuvant: Heating impacts the tumor microenvironment through intrinsic and extrinsic mechanisms, which could enhance immunotherapy. Increased vascular perfusion and blood flow to the tumor occurs through both thermoregulatory signals, as well as changes in tumor metabolism, leading to increased HIF-1, which leads to increased ROS production and VEGF expression. Increased trafficking of CD8+ T cells occurs through heat-induced increases in E/P selectin and ICAM-1 on tumor blood vessels; increased TCR signaling and differentiation of naïve T cells to effector cells. Increased tumor cell-surface expression of MICA/B and upregulation of the ligand NKG2D on NK cells, thereby increasing NK cell cytotoxic potential. Increased functional activity of macrophages, dendritic cells, Increased release of HSPs into the extracellular environment, which stimulate downstream immune activity, and increased antigen presentation.

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