荷兰莱顿大学医学中心Ton N. Schumacher研究组揭示CD8+ T细胞源性细胞因子在肿瘤微环境(TME)中的时空动态。2024年1月8日出版的《癌细胞》发表了这项成果。

他们描述了一种基于单细胞转录组的方法来推断单个细胞接收了哪些信号。他们证明，与预期相反，CD8+ T细胞衍生的干扰素γ (IFNγ)是相对于肿瘤坏死因子α (TNFα)的TME的主要修饰因子。此外，研究人员还发现，具有丰富IFNγ感知的细胞池的特征是转化生长因子β (TGFβ)诱导基因的表达减少，这与IFNγ介导的TME重塑一致。

总的来说，这些数据提供了CD8+ T细胞分泌的细胞因子应该分为局部和全局组织修饰因子的证据，并描述了一种广泛适用的方法来解剖细胞因子和趋化因子对TME的调节。

据悉，TME中的细胞通过分泌和感知可溶性介质(如细胞因子和趋化因子)相互影响。虽然IFNγ和TNFα的信号传导是抗肿瘤免疫反应不可或缺的一部分，但人们对这些细胞因子时空行为的理解有限。

附：英文原文

Title: Distinct spatiotemporal dynamics of CD8+ T cell-derived cytokines in the tumor microenvironment

Author: Mirjam E. Hoekstra, Maarten Slagter, Jos Urbanus, Mireille Toebes, Nadine Slingerland, Iris de Rink, Roelof J.C. Kluin, Marja Nieuwland, Ron Kerkhoven, Lodewyk F.A. Wessels, Ton N. Schumacher

Issue&Volume: 2024/01/08

Abstract: Cells in the tumor microenvironment (TME) influence each other through secretion and sensing of soluble mediators, such as cytokines and chemokines. While signaling of interferon γ (IFNγ) and tumor necrosis factor α (TNFα) is integral to anti-tumor immune responses, our understanding of the spatiotemporal behavior of these cytokines is limited. Here, we describe a single cell transcriptome-based approach to infer which signal(s) an individual cell has received. We demonstrate that, contrary to expectations, CD8+ T cell-derived IFNγ is the dominant modifier of the TME relative to TNFα. Furthermore, we demonstrate that cell pools that show abundant IFNγ sensing are characterized by decreased expression of transforming growth factor β (TGFβ)-induced genes, consistent with IFNγ-mediated TME remodeling. Collectively, these data provide evidence that CD8+ T cell-secreted cytokines should be categorized into local and global tissue modifiers, and describe a broadly applicable approach to dissect cytokine and chemokine modulation of the TME.

DOI: 10.1016/j.ccell.2023.12.010

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00438-5