美国麻省理工学院Tyler Jacks、Aviv Regev等研究人员合作发现，传统的I型树突状细胞在肿瘤引流淋巴结中维持着增殖性肿瘤抗原特异性TCF-1⁺CD8⁺T细胞的储存库。这一研究成果于2021年9月16日在线发表在国际学术期刊《免疫》上。

在肿瘤中，一个表达转录因子TCF-1的CD8⁺ T细胞亚群驱动着对免疫检查点阻断的反应。研究人员报道了在肺腺癌自发模型中维持这些细胞的机制。对肿瘤抗原特异性TCF-1⁺CD8⁺ T细胞的纵向取样和单细胞测序显示，虽然瘤内TCF-1⁺CD8⁺ T细胞获得了功能障碍的特征，并随着肿瘤的发展而数量减少，但肿瘤引流LN（dLN）的TCF-1⁺CD8⁺ T细胞频率保持稳定。

两个不连续的瘤内TCF-1⁺CD8⁺ T细胞亚群随时间发展，一个是增殖型SlamF6⁺亚群，一个是非循环型SlamF6^-亚群。阻断dLN的排出减少了瘤内SlamF6⁺TCF-1⁺CD8⁺ T细胞的频率。dLN中的常规I型树突状细胞（cDC1）的数量随着肿瘤的发展而减少，Flt3L⁺抗CD40治疗恢复了SlamF6⁺T细胞的频率并减少了肿瘤负担。因此，肿瘤dLN中的cDC1维持了一个TCF-1⁺CD8⁺ T细胞库，它们的减少导致了抗肿瘤免疫的失败。

附：英文原文

Title: Conventional type I dendric cells maintain a reservoir of proliferative tumor-antigen specific TCF-1+ CD8+ T cells in tumor-draining lymph nodes

Author: Jason M. Schenkel, Rebecca H. Herbst, David Canner, Amy Li, Michelle Hillman, Sean-Luc Shanahan, Grace Gibbons, Olivia C. Smith, Jonathan Y. Kim, Peter Westcott, William L. Hwang, William A. Freed-Pastor, George Eng, Michael S. Cuoco, Patricia Rogers, Jin K. Park, Megan E. Burger, Orit Rozenblatt-Rosen, Le Cong, Kristen E. Pauken, Aviv Regev, Tyler Jacks

Issue&Volume: 2021-09-16

Abstract: In tumors, a subset of CD8+ T cells expressing the transcription factor TCF-1 drives the response to immune checkpointblockade. We examined the mechanisms that maintain these cells in an autochthonousmodel of lung adenocarcinoma. Longitudinal sampling and single-cell sequencing oftumor-antigen specific TCF-1+ CD8+ T cells revealed that while intratumoral TCF-1+ CD8+ T cells acquired dysfunctional features and decreased in number as tumors progressed,TCF-1+ CD8+ T cell frequency in the tumor draining LN (dLN) remained stable. Two discrete intratumoralTCF-1+ CD8+ T cell subsets developed over time—a proliferative SlamF6+ subset and a non-cycling SlamF6 subset. Blocking dLN egress decreased the frequency of intratumoral SlamF6+ TCF-1+ CD8+ T cells. Conventional type I dendritic cell (cDC1) in dLN decreased in number withtumor progression, and Flt3L+anti-CD40 treatment recovered SlamF6+ T cell frequencies and decreased tumor burden. Thus, cDC1s in tumor dLN maintaina reservoir of TCF-1+ CD8+ T cells and their decrease contributes to failed anti-tumor immunity.

DOI: 10.1016/j.immuni.2021.08.026

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00360-5