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 Dong,Christine M. Lohse,Bradley C. Leibovich,Michael L. Blute,John C. Cheville,Eugene D. Kwon +6 more
TLDR
Interactions between immune cell PD-1 and B7-H1 may promote cancer progression by contributing to immune dysfunction in patients with RCC, and levels of immune cells expressingPD-1 were increased in Patients with high-risk RCC tumors.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 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.read more
Citations
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The PD-1 pathway in tolerance and autoimmunity
TL;DR: This review highlights how PD‐1 and its ligands defend against potentially pathogenic self‐reactive effector T cells by simultaneously harnessing two mechanisms of peripheral tolerance: (i) the promotion of Treg development and function and (ii) the direct inhibition of potentially pathogen self-reactive T cells that have escaped into the periphery.
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A guide to cancer immunotherapy: from T cell basic science to clinical practice.
TL;DR: This guide to cancer immunotherapy provides a comprehensive historical and biological perspective regarding the advent and clinical implementation of cancer immunotherapeutics, with an emphasis on the fundamental importance of T lymphocyte regulation.
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Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired.
Mojgan Ahmadzadeh,Laura A. Johnson,Bianca Heemskerk,John R. Wunderlich,Mark E. Dudley,Donald E. White,Steven A. Rosenberg +6 more
TL;DR: It is suggested that the tumor microenvironment can lead to up-regulation of PD-1 on tumor-reactive T cells and contribute to impaired antitumor immune responses.
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PD-1 and PD-1 ligands: from discovery to clinical application.
Taku Okazaki,Tasuku Honjo +1 more
TL;DR: The history ofPD-1 research since its discovery and recent findings that suggest promising future for the clinical application of PD-1 agonists and antagonists to various human diseases are summarized.
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The prognostic influence of tumour-infiltrating lymphocytes in cancer: a systematic review with meta-analysis
TL;DR: Any future studies should be carefully designed, to prevent overestimating the effect of TILs on prognosis, and ratios between TIL subsets may be more informative.
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Upregulation of PD-1 expression on HIV-specific CD8 + T cells leads to reversible immune dysfunction
Lydie Trautmann,Loury Janbazian,Loury Janbazian,Nicolas Chomont,Elias A. Said,Sylvain Gimmig,Benoit Bessette,Mohamed Rachid Boulassel,Eric Delwart,Homero Sepulveda,Robert Balderas,Jean-Pierre Routy,Jean-Pierre Routy,Elias K. Haddad,Elias K. Haddad,Rafick Pierre Sekaly,Rafick Pierre Sekaly +16 more
TL;DR: Blocking PD-1 engagement to its ligand (PD-L1) enhanced the capacity of HIV-specific CD8+ T cells to survive and proliferate and led to an increased production of cytokines and cytotoxic molecules in response to cognate antigen.
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