Fibrosarcoma cells expressing allogeneic MHC Class II antigens induce protective antitumor immunity

Abstract

The initiation of effective immune responses usually requires presentation of Ags by MHC class I and class II molecules. Although most tumors express MHC class I molecules, MHC class II molecule expression is generally limited to specialized APCs. One reason spontaneous tumors may fail to elicit effective immune responses is that tumor Ags are inefficiently presented by APCs, and adequate T cell-mediated help is not generated. To test this hypothesis, we investigated the possibility of enhancing Th cell stimulation by inducing expression of MHC class II molecules on tumor cells. We transfected a murine fibrosarcoma, Sa1N, with the genes encoding allogeneic (I-Ad) or syngeneic (I-Ak) MHC class II molecules. We then compared the tumorigenic and immunogeneic potential of these transfectants to parental Sa1N tumor cells. Subcutaneous injection of allogeneic or syngeneic transfectants resulted in dramatically fewer tumors than injection of unmodified fibrosarcoma cells, and mice inoculated with MHC class II gene-transfected cells were resistant to subsequent challenge with parental Sa1N cells. Rejection of allogeneic MHC class II Ag+ tumor cells could be mediated by either CD4+ or CD8+ T cells, whereas rejection of secondary challenge with wild-type Sa1N tumor cells required both T cell subsets. These results demonstrate that allogeneic, as well as syngeneic, MHC class II Ag+ tumor cells can stimulate protective antitumor immunity.