Purpose/objective(s) <p>This study aims to investigate the impact of partial blood volume FLASH irradiation on immune system in a mouse leg model.</p> Materials/methods <p>The right hind limbs of C57BL/6&#xa0;N mice were irradiated in a single fraction with an electron beam using either 50&#xa0;Gy/s (2&#xa0;Gy, 5&#xa0;Gy, 10&#xa0;Gy, 20&#xa0;Gy, delivery time 0.04 –0.4&#xa0;s) or 10&#xa0;Gy/s (5&#xa0;Gy, 10&#xa0;Gy, 15&#xa0;Gy, 20&#xa0;Gy, delivery time 0.5 –1.5&#xa0;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.</p> Results <p>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&#xa0;day post-irradiation. Generally, higher dose rate (50&#xa0;Gy/s) irradiation induced much less subsets depletion than lower dose rate (10&#xa0;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.</p> Conclusion <p>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.</p>

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

  • Xiaohang Qin,
  • Yinghui Li,
  • Peimeng You,
  • Yinuo Zhu,
  • Jian Wang,
  • Guangshan Wang,
  • Cuimeng Tian,
  • Feng-Ming Spring Kong,
  • Hao Zha,
  • Teng Ma,
  • Jian-Yue Jin

摘要

Purpose/objective(s)

This study aims to investigate the impact of partial blood volume FLASH irradiation on immune system in a mouse leg model.

Materials/methods

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.

Results

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.

Conclusion

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.