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

• Published in: Clinical cancer research 2007-03, Vol.13 (6), p.1757-1761
• Main Authors: THOMPSON, R. Houston, HAIDONG DONG, LOHSE, Christine M, LEIBOVICH, Bradley C, BLUTE, Michael L, CHEVILLE, John C, KWON, Eugene D
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antigens, CD - metabolism; Antineoplastic agents; Apoptosis Regulatory Proteins - metabolism; Biological and medical sciences; Carcinoma, Renal Cell - diagnosis; Carcinoma, Renal Cell - metabolism; Carcinoma, Renal Cell - mortality; Female; Humans; Immunotherapy; Kidney cancer; Kidney Neoplasms - diagnosis; Kidney Neoplasms - metabolism; Kidney Neoplasms - mortality; Kidneys; Lymphocyte Subsets - metabolism; Lymphocytes, Tumor-Infiltrating - metabolism; Male; Medical sciences; Middle Aged; Neoplasm; Nephrology. Urinary tract diseases; Pharmacology. Drug treatments; Prognosis; Programmed Cell Death 1 Receptor; Survival Analysis; T cell; Tumor biomarker; Tumors of the urinary system
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-06-2599

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 T cells. Levels of immune cells expressing PD-1 (PD-1 + ) in clinical RCC tumors have not been evaluated. Thus, we tested whether immune cell PD-1 expression is observed within aggressive RCC tumors. Experimental Design: Between 2000 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 − patients (risk ratio, 2.24; P = 0.004). Conclusions: Levels of immune cells expressing PD-1 were increased in patients with high-risk RCC tumors. Interactions between immune cell PD-1 and B7-H1 may promote cancer progression by contributing to immune dysfunction in patients with RCC.