Effects of different dose rates on tumor microenvironment in a mouse melanoma tumor model

The dose rate is an important variable that affects cell survival. With the introduction of modern accelerators and treatment techniques with high dose rate capacity, it has become important in external radiotherapy (RT) applications. Although the effects of dose rate on tumor cells are well defined, Its impact on the tumor microenvironment (TME), which is important phenomenon in cancer prognosis, recurrence, and treatment response, is unknown. An efficacy study of RT delivering 2 Gy and 10 Gy at 3 different dose rates (1 Gy/min, 6 Gy/min, 14 Gy/min) was performed in immunocompetent C57BL/6 mice carrying B16-F10 syngeneic tumors. On day 7 post-RT, the blood and tumor tissues of mice were harvested. The amount of DNA breakage in blood mononuclear cells and the histomorphological features of TME in tumor tissue were examined. Smaller tumor volume (p<0.01), decreased mitosis (p=0.01) and increased pleomorphism (p<0.01) in cancer cells were observed in the arm that received high-dose RT. The amount of DNA damage in the high and low dose arms was similar (p=0.65). No difference was found in terms of tumor growth, amount of DNA breakage, and TME histomorphological features at 3 different dose rates for each dose. With this study, we show that different dose rates do not cause different effects on TME in the malignant melanoma tumor model.