Tim-3 expression represents dysfunctional tumor infiltrating T cells in renal cell carcinoma |
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| Authors: | Chen Cai Yi-Fan Xu Zhen-Jie Wu Qin Dong Min-Yu Li Jason C. Olson Yaron M. Rabinowitz Lin-Hui Wang Yinghao Sun |
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| Affiliation: | 1.Department of Special Clinic, Changhai Hospital,Second Military Medical University,Shanghai,China;2.Department of Urology, Changhai Hospital,Second Military Medical University,Shanghai,China;3.Department of Urology, Changzheng Hospital,Second Military Medical University,Shanghai,China;4.Department of Nephrology, Shanghai Corps Hospital,Chinese People’s Armed Police Forces,Shanghai,China;5.Georgetown University School of Medicine,Washington,USA |
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| Abstract: | ![]()
PurposeRenal cell carcinoma (RCC) is the most common cancer of kidney. Evidences have shown that RCC is sensitive to various immunotherapies. Tim-3 plays a role in suppressing Th1-mediated immune responses. However, no study has yet examined the effect of Tim-3 on tumor infiltrating lymphocytes (TILs) in RCC.MethodsWe investigated the expression and function of Tim-3 on TIL CD4+ T cells and TIL CD8+ T cells from 30 RCC patients.ResultsLevels of Tim-3 were significantly increased on both TIL CD4+ T cells and TIL CD8+ T cells and were associated with higher stages of the cancer. Also, GATA-3 and interferon gamma (IFN-γ) were down-regulated, whereas T-bet was up-regulated in TIL Tim-3+ T cells, indicating that Tim-3 expression defined a population of dysfunctional TIL Th1/Tc1 cells. Mechanism analyses showed that TIL Tim-3-expressing CD8+ T cells exhibited impaired Stat5 and p38 signaling pathway. Blocking the Tim-3 pathway restored cell proliferation and increased IFN-γ production in TIL CD4+ and CD8+ T cells of RCC.ConclusionsThese results suggest that Tim-3 may be used as a novel target for increasing immune responses in RCC tumor microenvironment. |
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