The molecular mechanisms responsible for the high immunosuppressive capacity of CD4+ Tregs in tumors are not well known. High-dimensional single-cell profiling of T cells from chemotherapy-naive individuals with non-small-cell lung cancer identified the transcription factor IRF4 as specifically expressed by a subset of intratumoral CD4+ effector Tregs with superior suppressive activity. In contrast to the IRF4- counterparts, IRF4+ Tregs expressed a vast array of suppressive molecules, and their presence correlated with multiple exhausted subpopulations of T cells. Integration of transcriptomic and epigenomic data revealed that IRF4, either alone or in combination with its partner BATF, directly controlled a molecular program responsible for immunosuppression in tumors. Accordingly, deletion of Irf4 exclusively in Tregs resulted in delayed tumor growth in mice while the abundance of IRF4+ Tregs correlated with poor prognosis in patients with multiple human cancers. Thus, a common mechanism underlies immunosuppression in the tumor microenvironment irrespective of the tumor type.

中文翻译：

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IRF4 在人类癌症中指导效应 Treg 分化和免疫抑制。


CD4+ Tregs 在肿瘤中具有高免疫抑制能力的分子机制尚不清楚。对未经化疗的非小细胞肺癌患者的 T 细胞进行高维单细胞分析，发现转录因子 IRF4 由肿瘤内 CD4+ 效应 Treg 子集特异性表达，具有优异的抑制活性。与 IRF4- 对应物相比，IRF4+ Tregs 表达大量抑制性分子，它们的存在与多个耗尽的 T 细胞亚群相关。转录组和表观基因组数据的整合表明，IRF4无论是单独使用还是与其伙伴BATF组合，都直接控制负责肿瘤免疫抑制的分子程序。因此，仅删除Tregs中的Irf4会导致小鼠肿瘤生长延迟，而IRF4+ Tregs的丰度与多种人类癌症患者的不良预后相关。因此，无论肿瘤类型如何，肿瘤微环境中的免疫抑制都有一个共同的机制。