B7-1 ENHANCES NATURAL-KILLER CELL-MEDIATED CYTOTOXICITY AND INHIBITS TUMOR-GROWTH OF A POORLY IMMUNOGENIC MURINE CARCINOMA

The B7-1 molecule expressed on antigen presenting cells is an importan t costimulatory molecule for T cell activation. It has been demonstrat ed that murine B7-1 can enhance host immunity and lead to tumor reject ion via its costimulatory function. Here, we investigate how transfect ion of B7-1 into line 1, a poorly immunogenic murine lung carcinoma, a ffects the generation and function of different immune effector cells. Line 1 cells expressing B7-1 form tumors that grow at a slower rate t han the parental line 1. Our studies have shown that tumor infiltratin g lymphocytes present within the B7-1 expressing tumors are primarily composed of nonspecific killer cells with no specific cytotoxic T cell s present. To determine if increased nonspecific killer cells could in hibit the tumor growth of line 1 in the presence of B7-1, we examined the cytotoxicity of natural killer (NK) cells and lymphokine-activated killer (LAK) cells on the B7-1-transfected line 1 and the parental li ne 1. We found that B7-1 augments the NK- but not LAK-mediated killing against line 1 as measured in an in vitro Cr-51-release cytotoxicity assay. This enhancement could be blocked by CTLA-4 Ig. In vivo depleti on of NK cells led to growth of the B7-1-transfected line 1 at the sam e rate as the parental line 1. These results suggest that in addition to its costimulatory role for T cell activation B7-1 could be an acces sory molecule that intensifies NK-mediated cytotoxicity. This novel fi nding may provide a mechanism for the effect of B7-1 on tumors of low immunogenicity. (C) 1995 Academic Press, Inc.