IMPS-31FOCAL BRAIN RADIATION INDUCES SYSTEMIC LYMPHOPENIA IN MICE

Abstract

BACKGROUND: Approximately 40% of patients with high grade glioma (HGG) develop severe and prolonged lymphopenia after beginning standard radiation and concurrent temozolomide. This lymphopenia is associated with shortened survival. This animal model was developed to further evaluate the mechanisms behind radiation-induced lymphopenia. METHODS: 7-12 weeks old C57BL/6 and BALB/c mice received focal brain irradiation using the small animal radiation research platform (SARRP). Two radiation plans were studied: 2 Gy x 30 fractions or 4 Gy x 10 fractions. Blood was collected weekly via peripheral tail vein. Lymphocytes were labelled with antibodies to CD3, CD4, CD8 and CD45 and analyzed by Hemavet, Flow Cytometry and TruCount. RESULTS: In all four groups (n = 32) - C57BL/6 and BALB/c mice receiving prolonged and abbreviated schemes: 2 Gy x 30 fractions and 4 Gy x 10 fractions - lymphopenia was achieved but not sustained. C57BL/6 and BALB/c mice total lymphocyte counts decreased by 71% and 54% of baseline respectively, after 6 weeks of radiation. C57BL/6 and BALB/c mice total lymphocyte counts decreased by 80% and 64% of baseline respectively, after 2 weeks of radiation. Within 3 weeks of the completion of radiation, counts returned to 60-80% of baseline. CONCLUSION: This animal model demonstrates that focal radiation to a limited brain field is capable of inducing profound lymphopenia as is seen in patients with HGG. This radiation-induced lymphopenia occurs in either strain of mice, C57BL/6 and BALB/c. Unlike humans, this radiation-induced lymphopenia rapidly recovers after radiation is discontinued. Thus, this model provides an opportunity to investigate the mechanisms underlying etiology of radiation-induced lymphopenia but is not ideal to study interventions to improve the recovery of this lymphopenia. Additional studies are being conducted to further assess lymphocyte subtypes and cytokines.