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Lymphokine-induced killer (LAK) cells have shown preclinical in vitro and in vivo efficacy in the treatment of metastatic melanoma. However, there is a paucity of data describing the effects of irradiation on LAK activity. We have therefore investigated the effects of whole-body x-irradiation on the cytotoxicity of LAK cells against autologous metastatic melanoma cells. Lymphocytes were isolated from tumor-draining lymph nodes and the splenocytes of tumor-bearing C57BL/6 mice and subjected to an in vitro 4-h co-culture with the metastatic melanoma cell line A375. The cultured cells were washed and then reinfused into tumor-bearing mice. Twenty-four hours after reinfusion, the mice were either sham-irradiated or whole-body irradiated with a single dose of 7.5 Gy and 24 h later the LAK cells were reinfused. The A375 cells were also irradiated with either a single dose of 7.5 Gy or with two 5.0 Gy doses separated by 1 h before cell co-culture. The ability of LAK cells to lyse A375 cells 24 h after reinfusion was analyzed by either 51Cr release or FACS analysis. A single dose of whole-body irradiation (7.5 Gy) 24 h after LAK cell reinfusion ablated the cytotoxic activity of the LAK cells by approximately 90%. This loss in LAK activity was also detected when LAK cells were reinfused 24 h after whole-body irradiation with two 5.0 Gy doses of gamma-irradiation. No loss of cytotoxic activity was detected when LAK cells were cocultured with the A375 melanoma cells 24 h after x-irradiation. These data suggest that the protective effects of x-irradiation are, in part, due to the sensitization of autologous tumor
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