Possible involvement of immunologic factors in radiotherapy of mouse MM46 tumors, (1)

The therapeutic effect of irradiation to tumor is generally considered to be due to the tumor cell killing activity of radiation. However, progress in tumor immunology reveals that the immunological activity of the host also affects the tumor and the prognosis after radiotherapy. This study was carried out to clarify whether the anti-tumor cell-mediated immunity of host is more effectively induced by the combined use of cyclophosphamide with local irradiation than by simple local irradiation to the tumor. Cyclophosphamide is a drug which specifically suppresses the activity of suppressor T cells. MM46 tumors were inoculated into the left things of C3H/He mice (2 x 106 cells each) and then irradiated with a single dose of X-ray 7 or 8 days after inoculation. Cyclophosphamide was administered to a group of mice at various intervals before and/or after local irradiation. Tumor growth in vivo and in vitro was observed to evaluate the effect of cyclophosphamide on local irradiation. Suppression of tumor growth in the groups of mice treated with cyclophosphamide and irradiation was greater than that in the group of mice treated by irradiation alone, and the greatest suppression was observed in the mice treated with cyclophosphamide three days after irradiation for small tumors. However, in the groups treated with cyclophosphamide alone therapeutic result was not so effective. In an in vitro study, suppression of tumor growth was observed by cytostatic activity of the spleen cells from treated mice. The antitumor activity of spleen cells in the groups of mice treated with cyclophosphamide alone and cyclophosphamide with irradiation were greater than that in the groups of control mice and/or mice treated by irradiation alone. (J.P.N.)