EXPRESSION OF COSTIMULATORY MOLECULES BY TUMOR-CELLS DECREASES TUMORIGENICITY BUT MAY ALSO REDUCE SYSTEMIC ANTITUMOR IMMUNITY

Many tumor cells do not express co-stimulatory molecules, and this may account, in part, for their poor ability to stimulate T cells directl y, One strategy to enhance immune recognition would be to express such molecules on the tumor cell, Here, we show that expression of a membe r of the B7 family of co-stimulatory molecules by CMT93 murine colorec tal tumor or 1735 murine melanoma cells resulted in a local antitumor response in immunocompetent mice, The antitumor effect was diminished in athymic nude mice, indicating that T cells played an important part in this response, The ability of the B7-expressing tumor cells to gen erate systemic protective immunity was investigated by excision of tum ors that developed from the initial inoculation followed by rechalleng e with parental tumor cells, CMT93 is a poorly immunogenic tumor and n o significant systemic immunity was elicited by the expression of B7-1 in these cells, 1735 melanoma is a mildly immunogenic tumor, Unexpect edly, the systemic immunity obtained with 1735 tumors expressing B7-1 or B7-2 was weaker than that generated by parental 1735 cells (p < 0.0 01, stratified logrank test), even when coexpression of interferon-gam ma in the B7-1 cells produced high levels of surface MHC class I expre ssion, These results suggest that some caution is appropriate when con sidering the use of these molecules in the gene therapy of cancer.