X-irradiation to human malignant glioma cells enhances the cytotoxicity of autologous killer lymphocytes under specific conditions

PURPOSE: To clarify the effect of combining x-irradiation and human killer lymphocytes against autologous malignant glioma cells, we analyzed not only the alteration of surface antigen expression in irradiated tumor cells, but also the cytotoxic effects of human killer lymphocytes on the autologous tumor cells with and without x-irradiation. METHODS AND MATERIALS: Six malignant glioma cell-lines (MG 1-6) established from each patient with a malignant glioma in our institute, and U87MG, were used as materials. They were irradiated by 0-50 Gy of X-rays, and the alternations of their human histocompatability leukocyte antigen (HLA), HLA-ABC, HLA-DR, -DP, -DQ, and FAS expressions were examined. Then, three sets of autologous natural killer (NK) cells, and autologous tumor-specific T lymphocytes (ATTL) were induced from the peripheral blood mononuclear cells (PBMCs) of three patients, and in vitro cytotoxic effects of these killer cells on the irradiated autologous tumor cells were analyzed. RESULTS: Irradiation-enhanced HLA-DR, -DP, -DQ, and FAS expression in glioma cell lines with low p53 expression. However, there was no correlation between HLA-ABC expression and X-ray dose. After irradiation of the tumor cells, cytotoxicity was enhanced in four of six effectors; in particular, it was significantly elevated in two killer lymphocytes. It was speculated that the enhancing effect was influenced not only by the p53 status of the tumor, but also by the types of killer lymphocytes; the alteration of cytotoxicity in NK cells on irradiated tumor cells may be compensatory for alteration in ATTLs. CONCLUSION: It was indicated that irradiation of malignant tumor cells enhanced killer cell-mediated cytotoxicity in autologous models under specific conditions. These basic data should contribute to clinical trials using local radiotherapy and systemic adoptive immunotherapy with killer lymphocytes.