Local FLASH radiation exhibits a double-edged effect on the mouse immune system

This study aims to investigate the impact of partial blood volume FLASH irradiation on immune system in a mouse leg model. The right hind limbs of C57BL/6 N mice were irradiated in a single fraction with an electron beam using either 50 Gy/s (2 Gy, 5 Gy, 10 Gy, 20 Gy, delivery time 0.04 –0.4 s) or 10 Gy/s (5 Gy, 10 Gy, 15 Gy, 20 Gy, delivery time 0.5 –1.5 s). A total of 90 mice were used in the experiment, with five mice per dose/time group. T lymphocyte subsets (CD3+, CD4+, CD8+, naïve CD4+, and naïve CD8+) were analyzed in peripheral blood and spleen 1 and 4 days post-irradiation by flow cytometry. The dose response curves for the subset reduction can be well described by a sigmoid curve for subsets in both peripheral blood and spleen 1 day post-irradiation. Generally, higher dose rate (50 Gy/s) irradiation induced much less subsets depletion than lower dose rate (10 Gy/s) in peripheral blood, consistent with the simulation result that local FLASH radiotherapy may preserve immune cells in peripheral blood. Interestingly, the non-irradiated spleen also displayed substantial subset depletions with an opposite dose rate-dependent behavior. We speculate that radiation-induced red blood cell senescent may be responsible for this interesting phenomenon. The opposing dose rate–dependent responses in peripheral blood and splenic lymphocyte depletion highlight a dual effect of local FLASH irradiation: higher dose rates may protect circulating immune cells, yet may also potentially enhance damage to the lymphocytes in the spleen.