PD-1 is expressed by tumor-infiltrating immune cells and is associated with poor outcome for patients with renal cell carcinoma

Clin Cancer Res. 2007 Mar 15;13(6):1757-61. doi: 10.1158/1078-0432.CCR-06-2599.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / metabolism*
  • Apoptosis Regulatory Proteins / metabolism*
  • Carcinoma, Renal Cell / diagnosis*
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / mortality
  • Female
  • Humans
  • Kidney Neoplasms / diagnosis*
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / mortality
  • Lymphocyte Subsets / metabolism*
  • Lymphocytes, Tumor-Infiltrating / metabolism*
  • Male
  • Middle Aged
  • Prognosis
  • Programmed Cell Death 1 Receptor
  • Survival Analysis

Substances

  • Antigens, CD
  • Apoptosis Regulatory Proteins
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor