Article: article d'un périodique ou d'un magazine.
PD-1 is a regulator of NY-ESO-1-specific CD8+ T cell expansion in melanoma patients.
Journal of immunology
Date de publication
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't Publication Status: ppublish
The programmed death 1 (PD-1) receptor is a negative regulator of activated T cells and is up-regulated on exhausted virus-specific CD8(+) T cells in chronically infected mice and humans. Programmed death ligand 1 (PD-L1) is expressed by multiple tumors, and its interaction with PD-1 resulted in tumor escape in experimental models. To investigate the role of PD-1 in impairing spontaneous tumor Ag-specific CD8(+) T cells in melanoma patients, we have examined the effect of PD-1 expression on ex vivo detectable CD8(+) T cells specific to the tumor Ag NY-ESO-1. In contrast to EBV, influenza, or Melan-A/MART-1-specific CD8(+) T cells, NY-ESO-1-specific CD8(+) T cells up-regulated PD-1 expression. PD-1 up-regulation on spontaneous NY-ESO-1-specific CD8(+) T cells occurs along with T cell activation and is not directly associated with an inability to produce cytokines. Importantly, blockade of the PD-1/PD-L1 pathway in combination with prolonged Ag stimulation with PD-L1(+) APCs or melanoma cells augmented the number of cytokine-producing, proliferating, and total NY-ESO-1-specific CD8(+) T cells. Collectively, our findings support the role of PD-1 as a regulator of NY-ESO-1-specific CD8(+) T cell expansion in the context of chronic Ag stimulation. They further support the use of PD-1/PD-L1 pathway blockade in cancer patients to partially restore NY-ESO-1-specific CD8(+) T cell numbers and functions, increasing the likelihood of tumor regression.
Antigens, CD/biosynthesis, Antigens, CD/physiology, Antigens, Neoplasm/immunology, Apoptosis Regulatory Proteins/biosynthesis, Apoptosis Regulatory Proteins/physiology, CD8-Positive T-Lymphocytes/immunology, CD8-Positive T-Lymphocytes/metabolism, Cell Differentiation/immunology, Cell Line, Tumor, Cell Proliferation, Cytokines/biosynthesis, Epitopes, T-Lymphocyte/immunology, Humans, Lymphocyte Activation/immunology, Lymphocyte Count, Melanoma/immunology, Melanoma/metabolism, Membrane Proteins/antagonists & inhibitors, Membrane Proteins/immunology, Signal Transduction/immunology, Up-Regulation/immunology
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