Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor aggressiveness and potential therapeutic target

RH Thompson, MD Gillett, JC Cheville… - Proceedings of the …, 2004 - National Acad Sciences
RH Thompson, MD Gillett, JC Cheville, CM Lohse, H Dong, WS Webster, KG Krejci, JR Lobo…
Proceedings of the National Academy of Sciences, 2004National Acad Sciences
Expression of B7-H1, a costimulating glycoprotein in the B7 family, is normally restricted to
macrophage-lineage cells, providing a potential costimulatory signal source for regulation of
T cell activation. In contrast, aberrant expression of B7-H1 by tumor cells has been
implicated in impairment of T cell function and survival, resulting in defective host
antitumoral immunity. The relationship between tumor-associated B7-H1 and clinical cancer
progression is unknown. Herein, we report B7-H1 expression by both renal cell carcinoma …
Expression of B7-H1, a costimulating glycoprotein in the B7 family, is normally restricted to macrophage-lineage cells, providing a potential costimulatory signal source for regulation of T cell activation. In contrast, aberrant expression of B7-H1 by tumor cells has been implicated in impairment of T cell function and survival, resulting in defective host antitumoral immunity. The relationship between tumor-associated B7-H1 and clinical cancer progression is unknown. Herein, we report B7-H1 expression by both renal cell carcinoma (RCC) tumors of the kidney and RCC tumor-infiltrating lymphocytes. In addition, our analysis of 196 clinical specimens reveals that patients harboring high intratumoral expression levels of B7-H1, contributed by tumor cells alone, lymphocytes alone, or tumor and/or lymphocytes combined, exhibit aggressive tumors and are at markedly increased risk of death from RCC. In fact, patients with high tumor and/or lymphocyte B7-H1 levels are 4.5 times more likely to die from their cancer than patients exhibiting low levels of B7-H1 expression (risk ratio 4.53; 95% confidence interval 1.94–10.56; P < 0.001.) Thus, our study suggests a previously undescribed mechanism whereby RCC may impair host immunity to foster tumor progression. B7-H1 may prove useful as a prognostic variable for RCC patients both pre- and posttreatment. In addition, B7-H1 may represent a promising target to facilitate more favorable responses in patients who require immunotherapy for treatment of advanced RCC.
National Acad Sciences