Mild Hyperthermia Induced by Water-Filtered Infrared A Irradiation: A Potent Strategy to Foster Immune Recognition and Anti-Tumor Immune Responses in Superficial Cancers?

Apart from a number of positive “physiological” effects such as an increase in local blood flow which results in an improved oxygen supply and a reversal of tumor hypoxia, a key hallmark of cancer growth which greatly impairs anti-tumor immune responses, hyperthermia (HT) also exerts beneficial effects on anti-cancer immunity. The water-filtered infrared A (wIRA) irradiation technique achieves tissue temperatures in the fever-range (tT = 39–41 °C) or mild hyperthermia levels (tT = 39–43 °C) up to tissue depths of ≈25 mm in tissues. At tissue temperatures of 39–43 °C, by fostering the reactivity of the “immunological” TME [e.g., the activity of CD8⁺ cytotoxic T cells, CD4⁺ helper T cells, dendritic cells (DC), M1 macrophages, natural killer (NK) cells, and NK-like T (NK-T) cells], while compromising immunosuppressive cells [e.g., tumor-associated M2 macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), regulatory T (Treg) cells]. Moreover, elevated temperatures resulting in mild hyperthermia induce the synthesis and release of heat-shock proteins (HSPs), and thereby augment tumor antigenicity.