Modulation of killer cells induced by inoculation of irradiated tumor cells

There are two main radiation effects in therapy of malignant tumors, one is the direct cytotoxic effect of radiotherapy and the other is the immunological response in the host. To investigate the immunological response after radiation, activation and regulation of killer cells and cytokine activities were studied in an experimental tumor system using BALB/c mice and syngeneic Meth A fibrosarcoma. The mice inoculated with irradiated Meth A (Rad Meth A mice) acquired tumor-specific antitumor immunity as demonstrated by a tumor challenge test. The effector cells in Rad Meth A mice were mainly cytotoxic T lymphocytes (CTL). Moreover, the effector cells in the mice inoculated with Mitomycin C-treated Meth A (MMC Meth A mice) were also mainly CTL. The splenocytes of Rad Meth A mice and MMC Meth A mice produced Interleukin-2 (IL-2). Further, the responsiveness of splenocytes of Rad Meth A mice and MMC Meth A mice to IL-2 were increased in quantity. Ia-positive macrophages were increased in the spleen of Rad Meth A mice and MMC Meth A mice. These results suggest that Meth A treated with either X-ray or Mitomycin C can induce a specific antitumor immunological response in mice. When Rad Meth A mice and MMC Meth A mice were inoculated of Meth A again, Rad Meth A mice and MMC Meth A mice induced CTL activation. In addition to these findings, CTL activity was enhanced by i. p. administration of the anti-IL-1 antibody, the anti-IL-2 antibody and the anti-IL-6 antibody in mice. These results suggest that CTL activation is influenced by cytokines such as IL-1, IL-2 and IL-6. (author) 68 refs