PD-1 Is Expressed by Tumor-Infiltrating Immune Cells and Is Associated with Poor Outcome for Patients with Renal Cell Carcinoma

R. H. Thompson, H. Dong, C. M. Lohse, B. C. Leibovich, M. L. Blute, J. C. Cheville, E. D. Kwon
2007 Clinical Cancer Research  
Purpose: B7-H1 is expressed by clinically aggressive forms of renal cell carcinoma (RCC) and predicts adverse outcome. B7-H1 is known to impair host immunity via interaction with the Programmed Death-1 (PD-1) receptor, which is expressed by activated Tcells. Levels of immune cells expressing PD-1 (PD-1 + ) in clinical RCC tumors have not been evaluated. Thus, we tested whether immune cell PD-1expression is observed within aggressive RCC tumors. Experimental Design: Between 2000 and 2003, 267
more » ... 00 and 2003, 267 patients underwent nephrectomy at our institution for clear cell RCC and had fresh-frozen tissue available for review. These RCC specimens were immunostained using anti^PD-1 (clone MIH4) and outcome analyses were conducted. Results: Mononuclear immune cell infiltration was observed in 136 (50.9%) specimens. PD-1 + immune cells were present in 77 of these 136 (56.6%) tumors. In contrast, RCC tumor cells did not express PD-1. Patients with PD-1 + immune cells were significantly more likely to harbor B7-H1 + tumor cells (P < 0.001), larger tumors (P = 0.001), and tumors of higher nuclear grade (P = 0.001). Likewise, intratumoral PD-1 + immune cells were associated with advanced tumor-node-metastasis stage (P = 0.005), coagulative tumor necrosis (P = 0.027), and sarcomatoid differentiation (P = 0.008). With a median follow-up of 2.9 years, 52 patients died from RCC. Univariately, patients with PD-1 + immune cells were at significant risk of cancer-specific death compared with PD-1 À patients (risk ratio, 2.24; P = 0.004). Conclusions: Levels of immune cells expressing PD-1were increased in patients with high-risk RCC tumors. Interactions between immune cell PD-1and B7-H1may promote cancer progression by contributing to immune dysfunction in patients with RCC.
doi:10.1158/1078-0432.ccr-06-2599 pmid:17363529 fatcat:enfkrhr2zbeuhcxefahx7wy4we