Thermal regulation of dysbiotic tumor vasculature

Antibiotic use has substantially increased over the years. Although oral antibiotics treat infections, they also drastically change the gut microbiota, disturbing commensal bacteria that are essential for maintaining a number of homeostatic processes. Our recent published and unpublished work have shown that GI-tract dysbiosis causes drastic changes to the stroma of distal tumors, resulting in accelerated cancer progression of various solid tumors. We discovered that dysbiosis induces a significant suppression of adhesion molecules on tumor endothelial cells. Conversely, localized hyperthermia has been increasingly recognized to elicit various cellular responses, yet the effects of hyperthermia on the tumor vasculature during ABX-induced dysbiosis are unknown. We found that hyperthermia (60 min of either 41.5 °C or 43 °C, as compared to 37 °C) influenced various adhesion molecules to different degrees. Especially hyperthermic exposure of 43 °C for 1 hr was able to overcome the adhesion-molecule suppression found on the tumor vasculature during dysbiosis. Functional studies with splenocytes and T cells demonstrated that the induced increase in vasculature adhesion molecules caused increased tethering of leukocytes. Although further studies are warranted, these results demonstrate that hyperthermia exerts immune modulating effects and is capable of overcoming the dysbiosis-induced phenotype. Since current systemic anti-cancer treatments are often limited by their toxicities, localized hyperthermia may become a viable alternative in the future.