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 and͞or lymphocytes combined, exhibit aggressive tumors and are at markedly increased risk of death from RCC. In fact, patients with high tumor and͞or 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.costimulation ͉ immunotherapy ͉ T lymphocyte ͉ tumor biomarker

BACKGROUNDCancer cell expression of costimulatory molecule B7‐H1 has been implicated as a potent inhibitor of T‐cell–mediated antitumoral immunity. The authors recently reported that B7‐H1 is aberrantly expressed in primary renal cell carcinoma (RCC). Blockade of B7‐H1, as demonstrated in several murine cancer models, now represents a promising therapeutic target in RCC. However, the potential expression of B7‐H1 in metastatic RCC has not been investigated. In the current study, the authors updated their primary RCC results with additional follow‐up and investigated the potential role of B7‐H1 in metastatic RCC.METHODSBetween 2000 and 2004, 196 patients underwent nephrectomy and 26 patients had resection of RCC metastases for clear cell RCC. Immunohistochemical analysis was performed on tumor cryosections using a B7‐H1 monoclonal antibody (clone 5H1). A urologic pathologist quantified the percentage of B7‐H1–positive tumor cells and lymphocytes.RESULTSVariable levels of B7‐H1 were expressed on primary RCC tumor cells (n = 130 [66.3%]) and primary tumor‐infiltrating lymphocytes (n = 115 [58.7%]). Patients with high expression of B7‐H1 on primary tumor cells and/or lymphocytes were significantly more likely to die of RCC compared with patients with low B7‐H1 expression (risk ratio [RR] = 4.17; 95% confidence interval [95% CI], 1.97–8.84; P < 0.001) and this risk persisted in multivariate analysis after adjusting for the Mayo Clinic stage, size, grade, and necrosis score (RR = 2.63; 96% CI, 1.23–5.64; P = 0.013). Of the 26 metastatic specimens, cancer cell and lymphocyte B7‐H1 expression were demonstrated in 17 (65.4%) and 18 (69.2%) specimens, respectively. In total, 14 (54.3%) metastatic specimens had high aggregate B7‐H1 levels compared with 44.4% in primary RCC specimens.CONCLUSIONSPatients with RCC with high B7‐H1 expression were significantly more likely to die even after multivariate analysis. The authors also demonstrated that a high percentage of RCC metastases similarly harbored B7‐H1. The authors surmised that B7‐H1 blockade may augment current immunotherapy, including patients treated for metastases after cytoreductive nephrectomy. Cancer 2005. © 2005 American Cancer Society.

We found that patients 18 to 40 years old were more likely to have chromophobe and less likely to have clear cell RCC compared with patients 60 to 70 years old. We did not identify a higher incidence of papillary RCC in younger patients. Patients with clear cell RCC 18 to 40 years old had a higher incidence of low stage and cystic tumors compared with patients 60 to 70 years old, features which have been shown to have a favorable prognosis. These factors likely contributed to improved cancer specific survival for younger patients.