Abstract
Abstract Background: Approximately half of patients with solid tumors develop severe and prolonged lymphopenia after beginning standard radiation and this lymphopenia is associated with shortened survival. An animal model to understand the mechanisms behind radiation-induced lymphopenia has not previously been reported. Methods: Using the small animal radiation research platform (SARRP) C57BL/6 and BALB/c mice approximately 7-12 weeks old received focal brain irradiation with prolonged and abbreviated schemes: 2 Gy x 30 fractions and 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=12) - 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 72% and 63% of baseline respectively, after 6 weeks of radiation. C57BL/6 and BALB/c mice total lymphocyte counts decreased by 85% and 87% of baseline respectively, after 2 weeks of radiation. Within 3 weeks of the completion of radiation, counts returned to 60-80% of baseline. All animals had a similar magnitude of change in total lymphocyte counts. Conclusion: This animal model is a practical way to study the reduction in lymphocytes related to radiation. CD4 counts in BALB/c mice receiving prolonged radiation show a linear decline. Future immunology studies should assess T cell subsets and cytokines. The clinically observed phenomenon persistent radiation-induced lymphopenia is challenging to model in mice. Citation Format: Anna F. Piotrowski, Esteban Velarde, Stuart Grossman. Focal brain radiation induces systemic lymphopenia in an animal model. [abstract]. In: Proceedings of the AACR Special Conference: Advances in Brain Cancer Research; May 27-30, 2015; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2015;75(23 Suppl):Abstract nr B22.
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