Tim-3 expression represents dysfunctional tumor infiltrating T cells in renal cell carcinoma (Publication with Expression of Concern. See JAN, 2023)
Tim-3 expression represents dysfunctional tumor infiltrating T cells in renal cell carcinoma (Publication with Expression of Concern. See JAN, 2023)
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DOI：
10.1007/s00345-015-1656-7
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发表时间：
2016-04-01
影响因子：
3.4
通讯作者：
Sun, Yinghao
中科院分区：
文献类型：
--
作者：
Cai, Chen;Xu, Yi-Fan;Sun, Yinghao
肾细胞癌（RCC）是最常见的肾癌。有证据表明，RCC对各种免疫疗法都很敏感。Tim-3在抑制th1介导的免疫反应中发挥作用。然而，尚未有研究检测Tim-3对RCC中肿瘤浸润淋巴细胞（til）的影响。我们研究了Tim-3在30例RCC患者TIL CD4+ T细胞和TIL CD8+ T细胞上的表达和功能。TIL CD4+ T细胞和TIL CD8+ T细胞的Tim-3水平均显著升高，并与癌症的高分期相关。此外，在TIL Tim-3+ T细胞中，GATA-3和干扰素γ (ifn - γ)下调，而T-bet上调，表明Tim-3的表达定义了功能失调的TIL Th1/Tc1细胞群体。机制分析表明，表达TIL tim -3的CD8+ T细胞表现出Stat5和p38信号通路受损。阻断Tim-3通路可恢复RCC TIL CD4+和CD8+ T细胞的细胞增殖并增加ifn - γ的产生。这些结果提示Tim-3可能作为增强RCC肿瘤微环境免疫应答的新靶点。
Renal 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.We investigated the expression and function of Tim-3 on TIL CD4+ T cells and TIL CD8+ T cells from 30 RCC patients.Levels 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-gamma) 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-gamma production in TIL CD4+ and CD8+ T cells of RCC.These results suggest that Tim-3 may be used as a novel target for increasing immune responses in RCC tumor microenvironment.