近日，澳大利亚墨尔本大学教授Axel Kallies及其小组研究出淋巴结衍生的干细胞样而非肿瘤组织驻留的CD8⁺ T细胞可促进抗癌免疫。2025年7月29日出版的《自然—免疫学》发表了这项成果。

利用单细胞RNA测序和基因主题模型，该研究组系统地解剖了肿瘤和肿瘤引流淋巴结（tdLNs）中细胞毒性T细胞的异质性和功能。课题组发现肿瘤内TCF1⁺ T_PEX细胞及其后代获得了组织驻留程序，限制了它们对肿瘤控制和ICB反应的贡献。相比之下，MYB依赖的干细胞样TPEX细胞驻留在tdLNs中，维持CD8⁺ T细胞浸润到肿瘤中并介导ICB反应。细胞因子TGFβ是强制肿瘤内CD8⁺ T细胞驻留并限制tdLNs中干细胞样T_PEX细胞丰度的核心因素，从而抑制肿瘤控制。在人类癌症中发现了类似的具有前体和驻留特征的tgf β抑制瘤内和瘤外CD8⁺ T细胞网络。

研究人员表示，CD8⁺ T细胞介导的肿瘤控制和免疫检查点阻断（ICB）的有效性与衰竭T细胞（T_PEX）和组织驻留记忆T细胞的前体有关。然而，它们之间的关系和对肿瘤控制的相对贡献还不够清楚。

附：英文原文

Title: Lymph-node-derived stem-like but not tumor-tissue-resident CD8+ T cells fuel anticancer immunity

Author: Wijesinghe, Sharanya K. M., Rausch, Lisa, Gabriel, Sarah S., Galletti, Giovanni, De Luca, Marco, Qin, Lei, Wen, Lifen, Tsui, Carlson, Man, Kevin, Heyden, Leonie, Mason, Teisha, Newland, Lewis D., Kueh, Andrew, Liao, Yang, Chisanga, David, Swatler, Julian, Voulaz, Emanuele, Marulli, Giuseppe, Errico, Valentina, Losurdo, Agnese, Rossi, Gustavo R., Souza-Fonseca-Guimaraes, Fernando, Huntington, Nicholas D., Gebhardt, Thomas, Utzschneider, Daniel T., Herold, Marco J., Shi, Wei, Schroeder, Jan, Lugli, Enrico, Kallies, Axel

Issue&Volume: 2025-07-29

Abstract: CD8+ T cell-mediated tumor control and efficacy of immune checkpoint blockade (ICB) are associated with both precursors of exhausted T (TPEX) cells and tissue-resident memory T cells. Their relationships and relative contribution to tumor control, however, are insufficiently understood. Using single-cell RNA sequencing and genetic mouse models, we systematically dissected the heterogeneity and function of cytotoxic T cells in tumors and tumor-draining lymph nodes (tdLNs). We found that intratumoral TCF1+ TPEX cells and their progeny acquired a tissue-residency program that limits their contribution to tumor control and ICB response. By contrast, MYB-dependent stem-like TPEX cells residing in tdLNs sustained CD8+ T cell infiltration into tumors and mediated ICB response. The cytokine TGFβ was the central factor that enforced residency of intratumoral CD8+ T cells and limited the abundance of stem-like TPEX cells in tdLNs, thereby restraining tumor control. A similar network of TGFβ-constrained intratumoral and extratumoral CD8+ T cells with precursor and residency characteristics was found in human cancer.

DOI: 10.1038/s41590-025-02219-2

Source: https://www.nature.com/articles/s41590-025-02219-2