Development of carcinogen-induced skin tumors in mice with varied states of immune capacity.

The incidence of tumor formation in MCA-treated skin grafted onto maximally immunosuppressed mice that had been restored to varying extents with normal spleen cells was significantly greater in the mice with intermediate immune capacities than in those that had either minimal or maximal capacities. A similar biphasic tumor incidence curve was observed when MCA-treated skin was grafted onto mice of varying immune capacities, produced by thymectomy and varying doses of whole-body irradiation. Significantly more tumors occurred in the mice given moderate doses of irradiation than in tohse given higher or lower doses. That both of these procedures were actually able to induce discrete levels of immunocompetence was demonstrated by measuring skin allograft rejection times. The immunomodulated mice were observed to have skin graft rejection times which strongly correlated with the number of immunologically competent spleen cells transferred into them. The outgrowth potential of syngeneic normal mammary epithelial cells grafted into cleared mammary fat pads was similar in both immunologically altered and normal control mice, showing that immunoaltered and normal control mice were equally able to support the growth of transplanted normal tissues. These results, which conform with the predictions of the immunostimulation hypothesis, suggest that the immune response is able to stimulate as well as inhibit oncogenesis.