Crucial role of TNF-alpha in CD8 T cell-mediated elimination of 3LL-A9 Lewis lung carcinoma cells in vivo

The role of perforin, IFN-gamma, and TNF-alpha in anti-tumor CD8 T cell imm unity was examined in a new tumor model using a CD8 T cell epitope (GP33) d erived from lymphocytic choriomeningitis virus as a tumor-associated Ag. In contrast with parental 3LL-A9 (A9) Lewis lung carcinoma cells that progres sively grow in C57BL/6 mice, s.c. injection of GP33-transfected A9(GP33) tu mor cells induced a protective GP33-specific CD8 T cell response that led t o complete tumor cell elimination. Tumor regression was dependent on perfor in, IFN-gamma, or TNF-alpha, because A9(GP33) tumors developed in mice defi cient in one of these genes. A9(GP33) tumors arising in perforin- and IFN-g amma-deficient mice represented GP33 Ag-loss variants, demonstrating that G P33-specific CD8 T cells from these mice were able to exert an Ag selection pressure. In contrast, tumor cells growing in TNF-alpha knock-out mice sti ll expressed the tumor-associated GP33 peptide despite the presence of acti vated GP33-specific CD8 T cells. These findings provide evidence for a cruc ial role of TNF-alpha in A9 tumor cell elimination by CD8 T cells in vivo.