Effects of therapy with antineoplastic chemicals on the growth of tumors and the induction of cytotoxic T-cells in the spleens of treated hosts were studied in mice bearing syngeneic tumors, J774 macrophage tumor or EL-4 T-cell lymphoma. Progressively growing tumors suppressed the capacity for in vitro inducibility of spleen T-cells cytotoxic to allogeneic target cells. Doses of nitrogen mustard, mitomycin C, and polyinosinic-polycytidylic acid, which decreased the growth of J774, counteracted the tumor-induced suppression of in vitro cytotoxic T-cell induction in spleen cells from BALB/c mice. Higher doses of nitrogen mustard and polyinosinic-polycytidylic acid inhibited the ability of spleen T-cells to become cytotoxic even in tumor-free mice. 1-β-d-Arabinofuranosylcytosine and nitrogen mustard decreased the growth of EL-4 ascites tumor and simultaneously restored the cytotoxic T-cell function of spleen cells in C57BL/6J mice. Polyinosinic-polycytidylic acid inhibited the growth of EL-4 only weakly and did not relieve the tumor-induced suppression of cytotoxic T-cell response. The highest levels of nitrogen mustard and polyinosinic-polycytidylic acid decreased cytotoxic T-cell activity in normal C57BL/6J mice.
These results demonstrate the inhibitory effects of several chemotherapeutic drugs on tumor growth and simultaneously correlate with restoration of cell-mediated immunological reactivity.
Supported in part by National Cancer Institute Grants CA-08748, CA-16271, CA-17404, and CA-18856-02 and by National Science Foundation Grant PCM-75-19734.