TY - JOUR
T1 - A reassessment of the role of B7-1 expression in tumor rejection
AU - Wu, Tzyy Choou
AU - Huang, Alex Y.C.
AU - Jaffee, Elizabeth M.
AU - Levitsky, Hyam I.
AU - Pardoll, Drew M.
PY - 1995/11/1
Y1 - 1995/11/1
N2 - 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 co-stimulator in directly activating tumor specific, major histocompatibility complex 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 B7-1(hi) 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 B7-1(hi) 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 B7-1(hi) 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.
AB - 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 co-stimulator in directly activating tumor specific, major histocompatibility complex 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 B7-1(hi) 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 B7-1(hi) 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 B7-1(hi) 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.
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U2 - 10.1084/jem.182.5.1415
DO - 10.1084/jem.182.5.1415
M3 - Article
C2 - 7595212
AN - SCOPUS:0028861977
SN - 0022-1007
VL - 182
SP - 1415
EP - 1421
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 5
ER -