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PTPN2蛋白调控耗竭性T细胞的产生
2019-09-17 12:39

2019年9月16日,《自然—免疫学》在线发表了美国科学家的一项最新研究成果。来自哈佛医学院的W. Nicholas Haining、Arlene H. Sharpe等研究人员合作发现PTPN2蛋白能够调控耗竭的CD8阳性T细胞亚群的产生,并控制肿瘤免疫。

研究人员发现磷酸酶PTPN2作为终末耗竭亚群分化的新调控蛋白,其通过削减1型干扰素信号起作用。当淋巴细胞脉络丛脑膜炎病毒(lymphocytic choriomeningitis virus clone 13)感染时,CD8 阳性T细胞中Ptpn2的缺失增加了Tim-3阳性细胞的产生、增殖能力和细胞毒性,但没有改变Slamf6阳性细胞的数量。同样,CD8 阳性T细胞中的Ptpn2缺失增强了Tim-3阳性细胞的抗肿瘤反应并改善了对肿瘤的控制。在整个免疫系统中缺失Ptpn2导致MC38肿瘤的清除并且改善了PD-1对B16肿瘤的检查点阻断应答。这些研究结果表明,增加细胞毒性Tim-3/CD8双阳性T细胞的数量可以促进有效的抗肿瘤免疫,并将免疫细胞中的PTPN2作为一种有吸引力的癌症免疫治疗靶点。

据介绍,CD8 阳性T细胞耗竭是慢性病毒感染和癌症中出现的功能障碍状态,其特征在于通过未知机制形成Slamf6阳性祖细胞耗竭和Tim-3阳性终末耗竭亚群。

附:英文原文

Title: PTPN2 regulates the generation of exhausted CD8 + T cell subpopulations and restrains tumor immunity

Author: Martin W. LaFleur, Thao H. Nguyen, Matthew A. Coxe, Brian C. Miller, Kathleen B. Yates, Jacob E. Gillis, Debattama R. Sen, Emily F. Gaudiano, Rose Al Abosy, Gordon J. Freeman, W. Nicholas Haining, Arlene H. Sharpe

Issue&Volume: 2019-09-16

Abstract: 

CD8+ T cell exhaustion is a state of dysfunction acquired in chronic viral infection and cancer, characterized by the formation of Slamf6+ progenitor exhausted and Tim-3+ terminally exhausted subpopulations through unknown mechanisms. Here we establish the phosphatase PTPN2 as a new regulator of the differentiation of the terminally exhausted subpopulation that functions by attenuating type 1 interferon signaling. Deletion of Ptpn2 in CD8+ T cells increased the generation, proliferative capacity and cytotoxicity of Tim-3+ cells without altering Slamf6+ numbers during lymphocytic choriomeningitis virus clone 13 infection. Likewise, Ptpn2 deletion in CD8+ T cells enhanced Tim-3+ anti-tumor responses and improved tumor control. Deletion of Ptpn2 throughout the immune system resulted in MC38 tumor clearance and improved programmed cell death-1 checkpoint blockade responses to B16 tumors. Our results indicate that increasing the number of cytotoxic Tim-3+CD8+ T cells can promote effective anti-tumor immunity and implicate PTPN2 in immune cells as an attractive cancer immunotherapy target.

DOI: 10.1038/s41590-019-0480-4

Source: https://www.nature.com/articles/s41590-019-0480-4

Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:31.25
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex


本期文章:《自然—免疫学》:Online/在线发表

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