Expression of Tim-3 drives phenotypic and functional changes in Treg cells in secondary lymphoid organs and the tumor microenvironment.
Expression of Tim-3 drives phenotypic and functional changes in Treg cells in secondary lymphoid organs and the tumor microenvironment.
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Tim-3的表达驱动次级淋巴器官和肿瘤微环境中Treg细胞的表型和功能变化。
DOI：
10.1016/j.celrep.2021.109699
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发表时间：
2021-09-14
期刊：
影响因子：
8.8
通讯作者：
Kane LP
中科院分区：
文献类型：
--
作者：
Banerjee H;Nieves-Rosado H;Kulkarni A;Murter B;McGrath KV;Chandran UR;Chang A;Szymczak-Workman AL;Vujanovic L;Delgoffe GM;Ferris RL;Kane LP
调节性 T 细胞（Treg 细胞）是自我耐受的关键介质，但它们也会限制有效的抗肿瘤免疫。尽管在稳态下，淋巴器官中的一小部分 Treg 细胞表达假定的检查点分子 Tim-3，但该蛋白由更大比例的肿瘤浸润 Treg 细胞表达。使用驱动细胞类型特异性诱导型 Tim-3 表达的小鼠模型，我们发现 Treg 细胞表达 Tim-3 足以驱动 Treg 细胞达到更像效应器的表型，从而导致抑制活性、效应 T 细胞耗竭和肿瘤生长的增加。我们还表明，T-reg 细胞特异性诱导删除 Tim-3 可增强抗肿瘤免疫力。 Tim-3 对 Treg 细胞功能的增强与白细胞介素 10 (IL-10) 表达的增加以及向糖酵解代谢表型的转变密切相关。我们的数据表明 Tim-3+ Treg 细胞可能是治疗癌症的相关治疗靶细胞类型。调节性 T 细胞（Treg 细胞）限制对肿瘤的免疫反应，肿瘤浸润性 Treg 细胞尤其具有抑制性。然而，人们对 Treg 细胞功能增强的机制知之甚少。班纳吉等人。研究表明，在小鼠模型和癌症患者中，Tim-3 的表达可能通过细胞因子 IL-10 与 Treg 细胞抑制活性的增加有关。
Regulatory T cells (Treg cells) are critical mediators of self-tolerance, but they can also limit effective anti-tumor immunity. Although under homeostasis a small fraction of Treg cells in lymphoid organs express the putative checkpoint molecule Tim-3, this protein is expressed by a much larger proportion of tumor-infiltrating Treg cells. Using a mouse model that drives cell-type-specific inducible Tim-3 expression, we show that expression of Tim-3 by Treg cells is sufficient to drive Treg cells to a more effector-like phenotype, resulting in increases in suppressive activity, effector T cell exhaustion, and tumor growth. We also show that T-reg-cell-specific inducible deletion of Tim-3 enhances anti-tumor immunity. Enhancement of Treg cell function by Tim-3 is strongly correlated with increased expression of interleukin-10 (IL-10) and a shift to a more glycolytic metabolic phenotype. Our data demonstrate that Tim-3+ Treg cells may be a relevant therapeutic target cell type for the treatment of cancer. Regulatory T cells (Treg cells) limit the immune response to tumors, and tumor-infiltrating Treg cells are especially suppressive. However, the mechanisms underlying enhanced Treg cell function are poorly understood. Banerjee et al. show that Tim-3 expression is linked to increased Treg cell suppressive activity, possibly through the cytokine IL-10, in mouse models and people with cancer.
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影响因子：
5.4
作者：
Anderson, Ana C.;Lord, Graham M.;Dardalhon, Valerie;Lee, David H.;Sabatos-Peyton, Catherine A.;Glimcher, Laurie H.;Kuchroo, Vijay K.
通讯作者：
Kuchroo, Vijay K.
影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
TIM-3 表达是肿瘤组织中调节性 T 细胞的特征，并与肺癌进展相关
影响因子：
3.7
作者：
Gao X;Zhu Y;Li G;Huang H;Zhang G;Wang F;Sun J;Yang Q;Zhang X;Lu B
通讯作者：
Lu B
影响因子：
10.1
作者：
Anderson, Ana C.
通讯作者：
Anderson, Ana C.
影响因子：
5.4
作者：
Gautron, Anne-Sophie;Dominguez-Villar, Margarita;de Marcken, Marine;Hafler, David A.
通讯作者：
Hafler, David A.