Rejection of Mouse Renal Cell Carcinoma Elicited by Local Secretion of Interleukin‐2

Abstract

We introduced the interleukin-2 (IL-2) gene into mouse renal cell carcinoma (RenCa) in order to examine the mechanism of tumor rejection. IL-2 gene-transfected RenCa (RenCa/IL-2Hi) exhibited marked retardation of tumor growth when implanted in a syngeneic host. Growth retardation of RenCa/IL-2Hi was also observed in athymic nude mice even after depletion of natural killer (NK) cells by treatment with anti-asialo GM1 antibody. Histological analysis of RenCa/IL-2Hi tumors disclosed non-specific inflammatory changes in syngeneic hosts. Co-injection of Bacillus Calmette Guerin with RenCa/IL-2Hi considerably enhanced the anti-tumor effects. Taken together, these findings strongly suggest that in situ IL-2 production leads to tumor rejection through non-specific inflammatory responses without participation of T cells and NK cells. On the other hand, the syngeneic mice that had rejected RenCa/IL-2Hi acquired immunity against parental RenCa, suggesting possible participation of memory T cells in the second rejection of the tumor.