Longitudinal prediction of T and B lymphocyte kinetics following brain irradiation in rodents

Abstract Introduction Radiation-induced lymphopenia following brain-irradiation may influence tumor response to cancer treatment. Interactions between the immune system, tumor and radiotherapy manifest as global lymphopenia, and result in changes in B-lymphocyte and T-lymphocyte levels. We assessed the longitudinal effects of brain-irradiation on B-lymphocyte and T-lymphocyte concentrations in mice with and without glioblastoma. Methods C57BL/6 mice were either tumor-free or tumor-bearing with GL-261 glioma cells and underwent brain-irradiation with 2.5 Gy fractions in an 8-fraction irradiation regimen. We employed a tree-based model to analyze the acute impact of radiation and tumor volume on B-lymphocyte and T-lymphocyte reduction (total N=130). Next, we developed semi-mechanistic models to describe the recovery patterns of B-lymphocyte and T-lymphocyte post-depletion after brain irradiation in tumor-free rodents (N=40). Finally, we applied these models to predict B- and T-lymphocyte kinetics in tumor-bearing rodents. Results Brain irradiation induced a 50% reduction in B-lymphocyte and T-lymphocyte. Tumor volumes exceeding 59 mm³ caused B-lymphopenia but not T-lymphopenia during brain-irradiation. Radiation exposure of lymph nodes resulted in both B- and T-lymphopenia. Our models successfully described the recovery of B/T-lymphocytes following their depletion induced by irradiation. Simulations revealed that all mice experienced B-lymphopenia, with recovery occurring within 8 days. 80% of mice experienced T-lymphopenia, with an average recovery time of 3.6 days. When tumor volumes exceeding 59 mm³, mice suffered prolonged B-lymphopenia. Conclusion This study highlights the impact of lymph node radiation exposure and tumor volume on lymphocyte reduction and the utility of modeling in predicting long-term lymphocyte levels following brain irradiation.