PD-1 is a regulator of NY-ESO-1-specific CD8+ T cell expansion in melanoma patients.

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Serval ID
serval:BIB_46394FBFCFF4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
PD-1 is a regulator of NY-ESO-1-specific CD8+ T cell expansion in melanoma patients.
Journal
Journal of immunology
Author(s)
Fourcade J., Kudela P., Sun Z., Shen H., Land S.R., Lenzner D., Guillaume P., Luescher I.F., Sander C., Ferrone S., Kirkwood J.M., Zarour H.M.
ISSN
1550-6606 ([electronic])
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
182
Number
9
Pages
5240-5249
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
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.
Keywords
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
Pubmed
Web of science
Open Access
Yes
Create date
15/01/2010 15:20
Last modification date
20/08/2019 13:51
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