Cyclophosphamide-facilitated adoptive immunotherapy of an established tumor depends on elimination of tumor-induced suppressor T cells.
On the basis of preceding studies showing that tumor-induced, T cell-mediated immunosuppression serves as an obstacle to adoptive immunotherapy of the Meth A fibrosarcoma, it was predicted that cyclophosphamide treatment of tumor bearers would remove this obstacle and allow passively transferred immune T cells to cause tumor regression. It was found that infusion of immune spleen cells alone had no effect on tumor growth, and cyclophosphamide alone caused a temporary halt in tumor progression. In contrast, combination therapy consisting of intravenous injection of 100 mg/kg of cyclophosphamide followed 1 h later by intravenous infusion of tumor-immune spleen cells caused small, as well as large tumors, to completely and permanently regress. Tumor regression caused by combination therapy was completely inhibited by intravenous infusion of splenic T cells from donors with established tumors, but not by spleen cells from normal donors. These suppressor T cells were eliminated from the spleen by treating the tumor-bearing donors with 100 mg/kg of cyclophosphamide. Immune T cells, in contrast, were resistant to this dose of cyclophosphamide. These results show that failure of intravenously-infused, tumor-sensitized T cells to cause regression of the Meth A fibrosarcoma growing in its syngeneic or semi-syngeneic host is caused by the presence of a tumor-induced population of cyclophosphamide-sensitive suppressor T cells.
D000818:Animals; D002471:Cell Transformation, Neoplastic; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005354:Fibrosarcoma / Q000139:chemically induced / Q000188:drug therapy / Q000628:therapy*; D007116:Immunization, Passive; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000637:transplantation*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D008748:Methylcholanthrene; D003520:Cyclophosphamide