小柯机器人

加拿大多伦多综合医院David G. Brooks和Sabelo Lukhele共同合作近期取得重要工作进展，他们研究发现转录因子IRF2驱动干扰素介导的CD8⁺ T细胞衰竭以限制抗肿瘤免疫。相关论文2022年11月11日在线发表于《免疫》杂志上。

研究人员试图确定这些相反的程序是如何被差异诱导的。他们发现，转录因子干扰素调节因子2（IRF2）由肿瘤中的许多免疫细胞表达，以响应持续的IFN信号。CD8⁺ T细胞中IRF2的特异性缺失阻止了肿瘤内T细胞耗竭程序的获得，相反，启用了持续的效应功能，促进了长期的肿瘤控制，增加了对免疫检查点和过继细胞治疗的响应性。IRF2缺陷CD8⁺ T细胞的长期肿瘤控制需要IFN-I和IFN-II信号的持续整合。因此，IRF2是一种基本的反馈分子，它可以重新定向IFN信号来抑制T细胞反应，以增强癌症控制的潜在靶点。

据介绍，I型和II型干扰素（IFN）刺激对免疫激活至关重要的促炎程序，但也诱导免疫抑制反馈回路，阻碍对癌症生长的控制。

附：英文原文

Title: The transcription factor IRF2 drives interferon-mediated CD8+ T cell exhaustion to restrict anti-tumor immunity

Author: Sabelo Lukhele, Diala Abd Rabbo, Mengdi Guo, Jian Shen, Heidi J. Elsaesser, Rene Quevedo, Madeleine Carew, Ramy Gadalla, Laura M. Snell, Lawanya Mahesh, M. Teresa Ciudad, Bryan E. Snow, Annick You-Ten, Jillian Haight, Andrew Wakeham, Pamela S. Ohashi, Tak W. Mak, Weiguo Cui, Tracy L. McGaha, David G. Brooks

Issue&Volume: 2022-11-11

Abstract: Type I and II interferons (IFNs) stimulate pro-inflammatory programs that are criticalfor immune activation, but also induce immune-suppressive feedback circuits that impedecontrol of cancer growth. Here, we sought to determine how these opposing programsare differentially induced. We demonstrated that the transcription factor interferonregulatory factor 2 (IRF2) was expressed by many immune cells in the tumor in responseto sustained IFN signaling. CD8+ T cell-specific deletion of IRF2 prevented acquisition of the T cell exhaustion programwithin the tumor and instead enabled sustained effector functions that promoted long-termtumor control and increased responsiveness to immune checkpoint and adoptive celltherapies. The long-term tumor control by IRF2-deficient CD8+ T cells required continuous integration of both IFN-I and IFN-II signals. Thus, IRF2is a foundational feedback molecule that redirects IFN signals to suppress T cellresponses and represents a potential target to enhance cancer control.

DOI: 10.1016/j.immuni.2022.10.020

Source: https://www.cell.com/immunity/fulltext/S1074-7613(22)00561-1

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