美国科赫综合癌症研究所Stefani Spranger研究组发现，干扰素-γ（IFN-γ）的组织特异性丰度驱动调节性T（Treg）细胞抑制1型常规树突状细胞（DC1s）介导的细胞毒性T细胞对抗肺癌的启动。相关论文于2023年2月2日发表在《免疫》杂志上。

他们试图了解肿瘤引流纵隔淋巴结（mLN）特有的因素如何影响CD8 + T细胞对肺癌的反应。DC1显示出mLN特异性失败，无法诱导强大的细胞毒性T细胞反应。使用Treg细胞耗竭策略，他们发现Treg细胞在mLN内组织特异性微生态位内以空间协调的方式抑制DC1。Treg细胞抑制需要DC1和Treg细胞之间的MHC II依赖性接触。IFN-γ水平升高促使mLN中的Treg细胞分化为Th1样效应Treg细胞。在癌症患者中，Treg 细胞 Th1 极化，但 CD8+/Treg 细胞比值与检查点阻断免疫治疗反应不佳相关。因此，mLN中的IFN-γ使Treg细胞偏向为Th1样效应Treg细胞，驱动它们与DC1的密切相互作用并随后抑制细胞毒性T细胞反应。

据了解，局部环境因素影响LN中的 CD8+ T 细胞启动。

附：英文原文

Title: Tissue-specific abundance of interferon-gamma drives regulatory T cells to restrain DC1-mediated priming of cytotoxic T cells against lung cancer

Author: Maria Zagorulya, Leon Yim, Duncan M. Morgan, Austin Edwards, Elen Torres-Mejia, Noor Momin, Chloe V. McCreery, Izabella L. Zamora, Brendan L. Horton, James G. Fox, K. Dane Wittrup, J. Christopher Love, Stefani Spranger

Issue&Volume: 2023-02-02

Abstract: Local environmental factors influence CD8+ T cell priming in lymph nodes (LNs). Here, we sought to understand how factors uniqueto the tumor-draining mediastinal LN (mLN) impact CD8+ T cell responses toward lung cancer. Type 1 conventional dendritic cells (DC1s) showeda mLN-specific failure to induce robust cytotoxic T cells responses. Using regulatoryT (Treg) cell depletion strategies, we found that Treg cells suppressed DC1s in aspatially coordinated manner within tissue-specific microniches within the mLN. Tregcell suppression required MHC II-dependent contact between DC1s and Treg cells. Elevatedlevels of IFN-γ drove differentiation Treg cells into Th1-like effector Treg cellsin the mLN. In patients with cancer, Treg cell Th1 polarization, but not CD8+/Treg cell ratios, correlated with poor responses to checkpoint blockade immunotherapy.Thus, IFN-γ in the mLN skews Treg cells to be Th1-like effector Treg cells, drivingtheir close interaction with DC1s and subsequent suppression of cytotoxic T cell responses.

DOI: 10.1016/j.immuni.2023.01.010

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00020-1