Blockade of TIM3 relieves immunosuppression through reducing regulatory T cells in head and neck cancer.
Blockade of TIM3 relieves immunosuppression through reducing regulatory T cells in head and neck cancer.
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阻断 TIM3 可通过减少头颈癌中的调节性 T 细胞来缓解免疫抑制
DOI：
10.1186/s13046-018-0713-7
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发表时间：
2018-03-05
期刊：
影响因子：
--
通讯作者：
Sun ZJ
中科院分区：
文献类型：
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作者：
Liu JF;Wu L;Yang LL;Deng WW;Mao L;Wu H;Zhang WF;Sun ZJ
研究背景T细胞免疫球蛋白粘蛋白3（TIM 3）是一种负性免疫检查点，在肿瘤诱导的免疫抑制中起重要作用。然而，TIM 3在头颈部鳞状细胞癌（HNSCC）中调节免疫抑制的机制尚不十分清楚。通过组织学评分的定量分析，对TIM 3、Galectin-9、Foxp 3、CD 68和CD 163进行相关性分析。利用Tgfbr 1/Pten 2cKO HNSCC小鼠模型检测TIM 3对调节性T细胞（Treg）和巨噬细胞的影响。流式细胞术检测人宫颈鳞状细胞癌中Tregs、巨噬细胞和IFN-γ的含量。结果证明TIM 3/Galectin-9途径、调节性T细胞标志物（Foxp 3）和巨噬细胞标志物（CD 68、CD 163）在人宫颈鳞状细胞癌中密切相关。在转基因HNSCC小鼠模型中，通过抗TIM 3单克隆抗体阻断TIM 3诱导CD 4 + CD 25 + Foxp 3 + T细胞减少。同时，TIM 3 + T细胞的数量也减少。然而，CD 206+巨噬细胞的数量没有显著下降。抗TIM 3治疗小鼠后，CD 8 +T细胞上IFN-γ的产生增加，表明通过抑制这些负性免疫因子增强了抗肿瘤免疫应答。靶向TIM 3可以通过降低HNSCC中的TcR来增强抗肿瘤免疫应答。
BackgroundT-cell immunoglobulin mucin 3 (TIM3) is a negative immune checkpoint and plays a crucial part in tumor-induced immune suppression. However, the mechanism of TIM3 in regulating immunosuppression in head and neck squamous cell carcinoma (HNSCC) was still not quite clear.MethodsWe carried out the immunohistochemistry staining of HNSCC tissue microarrays. Through quantification of the histoscore, we performed the correlation analysis among the TIM3, Galectin-9, Foxp3, CD68 and CD163. The effects of TIM3 on regulatory T cells (Tregs) and macrophages were detected by utilizing theTgfbr1/Pten2cKO HNSCC mouse model. Flow cytometry were used to analysis the percent of Tregs, macrophages and IFN-γ.ResultsWe demonstrated the close association among TIM3/Galectin-9 pathway, regulatory T cell marker (Foxp3) and macrophage marker (CD68, CD163) in human HNSCC. In the transgenic HNSCC mouse model, blockade of TIM3 by the anti-TIM3 monoclonal antibody induced a reduction of CD4+CD25+Foxp3+Tregs. Meanwhile, the population of TIM3+Tregs was also decreased. However, the population of CD206+macrophages was not significantly declined. The increased IFN-γ production on CD8+T cells in anti-TIM3 treatment mice showed that the antitumor immune response was enhanced through suppression of these negative immune factors.ConclusionsThe present study demonstrated that TIM3 was associated with the immunosuppression in HNSCC. And targeting TIM3 can enhance anti-tumor immune response by decreasing Tregs in HNSCC.
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T 细胞免疫球蛋白粘蛋白 3 阻断可驱动头颈癌的抗肿瘤免疫反应
影响因子：
6.6
作者：
Liu JF;Ma SR;Mao L;Bu LL;Yu GT;Li YC;Huang CF;Deng WW;Kulkarni AB;Zhang WF;Sun ZJ
通讯作者：
Sun ZJ
DOI：
10.1038/nrc3239
发表时间：
2012-03-22
期刊：
Nature reviews. Cancer
影响因子：
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作者：
Pardoll DM
通讯作者：
Pardoll DM
影响因子：
15.1
作者：
Frisancho-Kiss, Sylvia;Coronado, Michael J.;Frisancho, J. Augusto;Lau, Vivian M.;Rose, Noel R.;Klein, Sabra L.;Fairweather, DeLisa
通讯作者：
Fairweather, DeLisa
影响因子：
10.1
作者：
Anderson, Ana C.
通讯作者：
Anderson, Ana C.
DOI：
10.1038/nri3073
发表时间：
2011-10-14
期刊：
Nature reviews. Immunology
影响因子：
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作者：
通讯作者：
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