CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
XCL1-XCR1 轴支持肠道组织驻留与抗肿瘤免疫
英文原题：The XCL1-XCR1 axis supports intestinal tissue residency and antitumor immunity.
查看英文原题
The XCL1-XCR1 axis supports intestinal tissue residency and antitumor immunity.
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中文摘要
组织驻留记忆T细胞（TRM）为抵御病原体和新兴恶性肿瘤提供前线保护。具有TRM特征的TIL（肿瘤浸润淋巴细胞）与改善的临床结局相关。然而，编程TRM分化和功能的细胞相互作用尚不十分清楚。利用小鼠遗传模型和靶向空间转录组学，我们发现CD8+ T细胞来源的趋化因子XCL1对TRM形成至关重要，且经典DC1（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促进了瘤内cDC1积累和T细胞持久性，从而改善了总生存期。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，我们已表明XCL1-XCR1轴在引导肠道CD8+ TRM空间分化和肿瘤控制中发挥非细胞自主作用。
展开英文摘要原文
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.
论文信息
- 作者
- Ferry A、Mempel KM、Monell A、Reina-Campos M、Scharping NE、Heeg M、Takehara KK、Schokrpur S
- 单位
- School of Biological Sciences, University of California, San Diego, La Jolla, CA, USA.United States
- 期刊
- The Journal of experimental medicine2025 Mar 3
- 原文标识
- PubMed 39841133 · DOI 10.1084/jem.20240776
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