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

R. Houston Thompson, Haidong M Dong, Christine M. Lohse, Bradley C. Leibovich, Michael L. Blute, John C. Cheville, Eugene D Kwon

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1757-1761
Number of pages5
JournalClinical Cancer Research
Volume13
Issue number6
DOIs
StatePublished - Mar 15 2007

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Renal Cell Carcinoma
Neoplasms
Cell Death
Death Domain Receptors
Nephrectomy
Immunity
Research Design
Necrosis
Clone Cells
Odds Ratio
Neoplasm Metastasis
T-Lymphocytes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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PD-1 is expressed by tumor-infiltrating immune cells and is associated with poor outcome for patients with renal cell carcinoma. / Thompson, R. Houston; Dong, Haidong M; Lohse, Christine M.; Leibovich, Bradley C.; Blute, Michael L.; Cheville, John C.; Kwon, Eugene D.

In: Clinical Cancer Research, Vol. 13, No. 6, 15.03.2007, p. 1757-1761.

Research output: Contribution to journalArticle

Thompson, R. Houston ; Dong, Haidong M ; Lohse, Christine M. ; Leibovich, Bradley C. ; Blute, Michael L. ; Cheville, John C. ; Kwon, Eugene D. / PD-1 is expressed by tumor-infiltrating immune cells and is associated with poor outcome for patients with renal cell carcinoma. In: Clinical Cancer Research. 2007 ; Vol. 13, No. 6. pp. 1757-1761.
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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.",
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T1 - PD-1 is expressed by tumor-infiltrating immune cells and is associated with poor outcome for patients with renal cell carcinoma

AU - Thompson, R. Houston

AU - Dong, Haidong M

AU - Lohse, Christine M.

AU - Leibovich, Bradley C.

AU - Blute, Michael L.

AU - Cheville, John C.

AU - Kwon, Eugene D

PY - 2007/3/15

Y1 - 2007/3/15

N2 - 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.

AB - 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.

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