IFN-γ- and Cell-to-Cell Contact-Dependent Cytotoxicity of Allograft-Induced Macrophages Against Syngeneic Tumor Cells and Cell Lines: An Application of Allografting to Cancer Treatment

Abstract

Abstract In allogeneic tumor or skin transplantation, the rejection process that destroys the allogeneic cells leaves syngeneic cells intact by discrimination between self and nonself. Here, we examined whether the cells infiltrating into the allografts could be cytotoxic against syngeneic immortal cells in vitro and in vivo. The leukocytes (i.e., macrophages (Mφ; 55–65% of bulk infiltrates), granulocytes (20–25%), and lymphocytes (15–20%)) infiltrating into allografts, but not into autografts, in C57BL/6 mice were cytotoxic against syngeneic tumor cells and cell lines, whereas the cytotoxic activity was hardly induced in allografted, IFN-γ−/− C57BL/6 mice. Among the leukocytes, Mφ were the major population of cytotoxic cells; and the cytotoxic activity appeared to be cell-to-cell contact dependent. When syngeneic tumor cells were s.c. injected into normal C57BL/6 mice simultaneously with the Mφ-rich population or allogeneic, but not syngeneic, fibroblastic cells, tumor growth was suppressed in a cell number-dependent manner, and tumor cells were rejected either with a Mφ:tumor ratio of about 30 or with an allograft:tumor ratio of ∼200. In the case of IFN-γ−/− C57BL/6 mice, however, the s.c. injection of the allograft simultaneously with tumor cells had no effect on the tumor growth. These results suggest that allograft or allograft-induced Mφ may be applicable for use in cancer treatment and that IFN-γ induction by the allograft may be crucial for the treatment.