Ferry Amir, Mempel Kianoosh M, Monell Alexander, Reina-Campos Miguel, Scharping Nicole E, Heeg Maximilian, Takehara Kennidy K, Schokrpur Shiruyeh, Kuo Ning, Saddawi-Konefka Robert, Gutkind J Silvio, Goldrath Ananda W
School of Biological Sciences, University of California, San Diego, La Jolla, CA, USA.
La Jolla Institute for Immunology , La Jolla, CA, USA.
J Exp Med. 2025 Mar 3;222(2). doi: 10.1084/jem.20240776. Epub 2025 Jan 22.
Tissue-resident memory T cells (TRM) provide frontline protection against pathogens and emerging malignancies. Tumor-infiltrating lymphocytes (TIL) with TRM features are associated with improved clinical outcomes. However, the cellular interactions that program TRM differentiation and function are not well understood. Using murine genetic models and targeted spatial transcriptomics, we found that the CD8+ T cell-derived chemokine XCL1 is critical for TRM formation and conventional DC1 (cDC1) supported the positioning of intestinal CD8+ T cells during acute viral infection. In tumors, enforced Xcl1 expression by antigen-specific CD8+ T cells promoted intratumoral cDC1 accumulation and T cell persistence, leading to improved overall survival. Notably, analysis of human TIL and TRM revealed conserved expression of XCL1 and XCL2. Thus, we have shown that the XCL1-XCR1 axis plays a non-cell autonomous role in guiding intestinal CD8+ TRM spatial differentiation and tumor control.
组织驻留记忆T细胞（TRM）为抵御病原体和新出现的恶性肿瘤提供一线保护。具有TRM特征的肿瘤浸润淋巴细胞（TIL）与改善的临床结果相关。然而，调控TRM分化和功能的细胞间相互作用尚不清楚。利用小鼠遗传模型和靶向空间转录组学，我们发现CD8 + T细胞衍生的趋化因子XCL1对TRM形成至关重要，并且传统的1型树突状细胞（cDC1）在急性病毒感染期间支持肠道CD8 + T细胞的定位。在肿瘤中，抗原特异性CD8 + T细胞强制表达Xcl1可促进肿瘤内cDC1积累和T细胞持久性，从而改善总生存期。值得注意的是，对人类TIL和TRM的分析揭示了XCL1和XCL2的保守表达。因此，我们已经表明，XCL1-XCR1轴在指导肠道CD8 + TRM空间分化和肿瘤控制中发挥非细胞自主作用。
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