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Cell Immunol. 2017 Mar;313:43-51. doi: 10.1016/j.cellimm.2017.01.001. Epub 2017 Jan 5.

Tumor antigen-specific CD8+ T cells are negatively regulated by PD-1 and Tim-3 in human gastric cancer.

Author information

1
Department of Oncology, Beijing Biohealthcare Biotechnology Co., Ltd, China.
2
Department of Internal Medicine, The Chinese Academy of Medical Sciences Tumor Hospital, China.
3
Department of Agricultural Science Research Institute, Guangzhou Zengcheng District, China.
4
Department of Oncology, Beijing Biohealthcare Biotechnology Co., Ltd, China. Electronic address: ljwgirl361@163.com.

Abstract

Cytotoxic CD8 T lymphocytes that are present in tumors and capable of recognizing tumor epitopes are nevertheless generally important in eliciting tumor rejection. NY-ESO-1 is a major target of CD8+ T cell recognition in gastric cancer (GC) and is among the most immunogenic tumor antigens defined to date. Thus, identifying the immune escape mechanisms responsible for inducing tumor-specific CD8+ T cell dysfunction may reveal effective strategies for immunotherapy. In an effort to understand in vivo tolerance mechanisms, we assessed the phenotype and function of NY-ESO-1-specific CD8+ T cells derived from peripheral blood lymphocytes (PBLs) and tumor-associated lymphocytes (TALs) of GC patients. Here, we report that Tim-3 expression defines a subpopulation of PD-1+ exhausted NY-ESO-1-specific CD8+ T cell and PD-1+Tim-3+ CD8+ T cells represented the largest subset of NY-ESO-1-specific CD8+ T cells in GC patients. Functionally, CD8+PD-1+Tim-3+ T cells were more impaired in IFN-γ, TNF-α and IL-2 production compared with PD-1+Tim-3- or PD-1-Tim-3- subsets. Dual blockade of Tim-3 and PD-1 during T-cell priming efficiently augmented proliferation and cytokine production by NY-ESO-1-specific CD8+ T cells could potentially be improved by therapeutic targeting of these inhibitory receptors, indicating that antitumor function of NY-ESO-1-specific CD8+ T cells could potentially be improved by therapeutic targeting of these inhibitory receptors.

KEYWORDS:

CD8(+) T cells; PD-1; Tim-3; Tumor-associated lymphocytes

PMID:
28110884
DOI:
10.1016/j.cellimm.2017.01.001
[Indexed for MEDLINE]

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