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PURPOSE: Glioblastoma (GB) and x-ray-based radiation therapy are associated with lymphopenia, which worsens prognosis and impairs antitumor immunity. Proton therapy, with its dosimetric properties that spare healthy brain tissue, is an alternative to reduce radiotoxicity. This study examined the effects of brain irradiation with x-rays or protons on lymphopenia. METHODS AND MATERIALS: We used GL261-tumor-bearing and tumor-free mice models to evaluate various lymphoid and myeloid cell populations after brain irradiation, assessing volume of brain irradiation, beam orientation, and lymphopenia onset timing via flow cytometry. RESULTS: B cells in the cervical lymph nodes but did not affect the spleen. Plasma cytokine levels in the interleukin 1 and macrophage inflammatory protein families correlated with leucocyte changes following exposure to both particle types. CONCLUSIONS: We describe that proton therapy resulted in less lymphopenia than proton radiation, and propose that the mechanism may be related to biological processes rather than solely decreased exposure of circulating lymphocytes. This may be used to guide the incorporation of immune therapy in GB. SYNOPSIS: Understanding how brain irradiation affects circulating immunity can inform strategies to improve brain tumor treatment. This involves combining irradiation with immunotherapy and adjusting clinical protocols to restore lymphocytes/boost antitumor T cells.
Coupey et al. (Thu,) studied this question.