小柯机器人

希腊雅典生物医学研究基金会Panayotis Verginis研究组揭示了IL-33在调节性T细胞（T_reg）介导的肿瘤免疫逃逸中的内在作用。相关论文在线发表在2019年12月16日的《自然—免疫学》上。

研究人员发现在稳定T_reg细胞功能过程中，警报蛋白白介素（IL）-33的细胞内在作用。具体而言，IL-33缺失的T_reg细胞在体内抑制作用减弱，并通过抑制肿瘤抑制素2受体（ST2）（IL-33受体）独立的方式促进肿瘤消失。在受到激活后，Il33^-/-T_reg细胞发生表观重编程，Ifng基因座的染色质可及性增加，通过核因子（NF）-κB-T-bet依赖的方式增加干扰素（IFN）-γ的产生。 IFN-γ对于T_reg细胞功能缺陷至关重要，因为其缺失可恢复Il33^-/-T_reg细胞的抑制性。重要的是，Il33基因缺失增强了免疫疗法的治疗效果。该研究揭示了癌症中，IL-33在维持T_reg细胞的稳定性以及其在治疗上重要内在作用。

据了解，T_reg细胞在肿瘤中的聚集阻碍了癌症免疫疗法的有效性。然而，靶向T_reg细胞的治疗具有有限的功效或导致自身免疫的发生。然而，对肿瘤中T_reg细胞稳定性的分子机制仍知之甚少。

附：英文原文

Title: An intrinsic role of IL-33 in T reg cell–mediated tumor immunoevasion

Author: Aikaterini Hatzioannou, Aggelos Banos, Theodore Sakelaropoulos, Constantinos Fedonidis, Maria-Sophia Vidali, Maren Khne, Kristian Hndler, Louis Boon, Ana Henriques, Vasiliki Koliaraki, Panagiotis Georgiadis, Jerome Zoidakis, Aikaterini Termentzi, Marc Beyer, Triantafyllos Chavakis, Dimitrios Boumpas, Aristotelis Tsirigos, Panayotis Verginis

Issue&Volume: 2019-12-16

Abstract: Regulatory T (Treg) cells accumulate into tumors, hindering the success of cancer immunotherapy. Yet, therapeutic targeting of Treg cells shows limited efficacy or leads to autoimmunity. The molecular mechanisms that guide Treg cell stability in tumors remain elusive. In the present study, we identify a cell-intrinsic role of the alarmin interleukin (IL)-33 in the functional stability of Treg cells. Specifically, IL-33-deficient Treg cells demonstrated attenuated suppressive properties in vivo and facilitated tumor regression in a suppression of tumorigenicity 2 receptor (ST2) (IL-33 receptor)-independent fashion. On activation, Il33/ Treg cells exhibited epigenetic re-programming with increased chromatin accessibility of the Ifng locus, leading to elevated interferon (IFN)-γ production in a nuclear factor (NF)-κB–T-bet-dependent manner. IFN-γ was essential for Treg cell defective function because its ablation restored Il33/ Treg cell-suppressive properties. Importantly, genetic ablation of Il33 potentiated the therapeutic effect of immunotherapy. Our findings reveal a new and therapeutically important intrinsic role of IL-33 in Treg cell stability in cancer.

DOI: 10.1038/s41590-019-0555-2

Source: https://www.nature.com/articles/s41590-019-0555-2

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
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