A reassessment of the role of B7-1 expression in tumor rejection.
Introduction of the B7-1 gene into murine tumor cells can result in rejection of the B7-1 transductants and, in some cases, systemic immunity to subsequent challenge with the nontransduced tumor cells. These effects have been largely attributed to the function of B7-1 as a costimulator in directly activating tumor specific, major histocompatibility class I-restricted CD8+ T cells. We examined the role of B7-1 expression in the direct rejection as well as in the induction of systemic immunity to a nonimmunogenic murine tumor. B-16 melanoma cells with high levels of B7-1 expression did not grow in C57BL/6 recipient mice, while wild-type B-16 cells and cells with low B7-1 expression grew progressively within 21 d. In mixing experiments with B7-1hi and wild-type B-16 cells, tumors grew out in vivo even when a minority of cells were B7-1-. Furthermore, the occasional tumors that grew out after injection of 100% B-16 B7-1hi cells showed markedly decreased B7-1 expression. In vivo antibody depletions showed that NK1.1 and CD8+ T cells, but not CD4+ T cells, were essential for the in vivo rejection of tumors. Animals that rejected B-16 B7-1hi tumors did not develop enhanced systemic immunity against challenge with wild-type B-16 cells. These results suggest that a major role of B7-1 expression by tumors is to mediate direct recognition and killing by natural killer cells. With an intrinsically nonimmunogenic tumor, this direct killing does not lead to enhanced systemic immunity.
Wu
T C
TC
Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21287, USA.
Huang
A Y
AY
Jaffee
E M
EM
Levitsky
H I
HI
Pardoll
D M
DM
D000818:Animals; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D015972:Gene Expression Regulation, Neoplastic; D006084:Graft Rejection / Q000276:immunology*; D007111:Immunity, Cellular; D007694:Killer Cells, Natural / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology*; D008546:Melanoma, Experimental / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D009368:Neoplasm Transplantation / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000637:transplantation
D018122:B7-1 Antigen; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins