Combination Therapy of Intravenously Injected Microglia and Radiation Therapy Prolongs Survival in a Rat Model of Spontaneous Malignant Glioma

Abstract

The aim of this study was to investigate the efficacy of combination therapy with intravenously injected microglia (MI) and radiation therapy (RT) for malignant glioma in rats. Transgenic rats expressing v-erbB and spontaneously developing malignant glioma were used. The rats were divided into 4 groups: control (n=19), RT alone (n=10), MI alone (n=9), and combination MI and RT (MI+RT) (n=10). Cranial x-ray irradiation (8Gy per fraction; once per week) was performed at 50 and 51weeks of age. Cultured rat microglial cells (5×106cells/rat) were intravenously injected via the tail vein within 30minutes after RT. No evidence of side effects, including thrombosis or graft-versus-host disease, was noted. Rats treated with RT alone, MI alone, MI+RT, and control survived 60.9, 56.3, 66.0, and 56.1weeks, respectively. The survival period of MI+RT was significantly longer than that of control (P=.014), MI alone (P=.027), and RT alone (P=.049). Immunohistochemical analysis showed a significantly higher number of tumor-infiltrated MI in the RT alone (P=.041) and MI+RT groups (P=.014) compared with the control. Significantly more CD8-positive lymphocytes were observed in the MI+RT group (P=.049) compared with the control. A positive correlation was found between the number of MI and CD8-positive lymphocytes (R2=0.556). A positive correlation was also found between CD8-positive lymphocytes and survival periods (R2=0.460). MI+RT increased infiltrated MI and CD8-positive T cells and prolonged survival in transgenic rats that spontaneously developed malignant glioma. Combined immunocellular therapy and RT may provide a novel treatment strategy for malignant glioma.