Harnessing the Circadian Clock to Alleviate Ionizing Radiation-Induced Toxicity During Melanoma Therapy

It is known that radiation therapy RT targeted to tumors especially melanomas can generate an in-situ tumor vaccine. In other words, inducing the release of antigens during cancer cell death, in association with proinflammatory signals, trigger the adaptive immune system to activate tumor-specific T cells and enhance tumor cell killing. The immune response of RT is especially pronounced in combination with immunotherapy. With our vivo experiments, we have used genetically mutant circadian clock disrupted Per12-- mice and rotating shift mice showed a decreased adaptive immune response compared to their wild-type counterparts as an indication of 2-3 fold reduced CD4 T lymphocytes in blood. In conclusion, these results suggest that circadian clock plays an important role in protecting host adaptive immune response which is important for efficient tumor cell killing against RT. In addition, we have established a circadian synchronization protocol in vitro using B16-F10 melanoma cell lines.