کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5530763 | 1549386 | 2017 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Research paperTumor antigen-specific CD8+ T cells are negatively regulated by PD-1 and Tim-3 in human gastric cancer Research paperTumor antigen-specific CD8+ T cells are negatively regulated by PD-1 and Tim-3 in human gastric cancer](/preview/png/5530763.png)
- 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.
- Tumor-derived NY-ESO-1-specific CD8+ T cells enriched coexpression of PD-1 and Tim-3 demonstrated impaired effector function.
- Dual blockade of PD-1 and Tim-3 pathways may allow for a more comprehensive reversal of tumor-induced T cell exhaustion, potentially leading to potent combination therapies.
- Antitumor T-cell function could potentially be improved by therapeutic targeting of these inhibitory receptors in human gastric cancer.
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-3â or PD-1âTim-3â 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.
Journal: Cellular Immunology - Volume 313, March 2017, Pages 43-51