In vivo labeling reveals continuous trafficking of TCF-1+ T cells between tumor and lymphoid tissue.
In vivo labeling reveals continuous trafficking of TCF-1+ T cells between tumor and lymphoid tissue.
复制标题
体内标记显示TCF-1+ T细胞在肿瘤和淋巴组织之间持续运输。
DOI：
10.1084/jem.20210749
复制
发表时间：
2022-06-06
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
肿瘤内T细胞亚群在募集或保留方面的差异尚不清楚。在这项研究中，光转换被用来暂时标记肿瘤浸润淋巴细胞，揭示了TCF-1+ T细胞在肿瘤和引流淋巴组织之间的连续迁移。提高免疫检查点疗法的疗效需要更好地了解免疫细胞如何在肿瘤中招募和维持。在这里，我们使用肿瘤免疫细胞区室的光转换来识别新进入的淋巴细胞，确定它们如何随时间变化，并研究它们从肿瘤中的排出。结合单细胞转录组学和流式细胞术，我们发现，虽然CD 8 T细胞亚群的多样性混合物进入肿瘤，但在这种环境中保留超过72小时的所有CD 8 T细胞都发展出耗尽的表型，揭示了该程序的快速建立。表达TCF-1并包括记忆细胞和干细胞样细胞的非效应子亚群没有形成肿瘤驻留细胞群，而是被连续招募到肿瘤中，但这种招募通过同时流出到肿瘤引流淋巴结来平衡。因此，肿瘤中的TCF-1+ CD 8 T细胞小生境是高度动态的，肿瘤和外周淋巴组织之间的细胞循环桥接全身和肿瘤内反应。
How intratumoral T cell subsets differ in their recruitment or retention is unclear. In this study, photoconversion is used to temporally label tumor-infiltrating lymphocytes, revealing the continuous migration of TCF-1+ T cells between the tumor and draining lymphoid tissue. Improving the efficacy of immune checkpoint therapies will require a better understanding of how immune cells are recruited and sustained in tumors. Here, we used the photoconversion of the tumor immune cell compartment to identify newly entering lymphocytes, determine how they change over time, and investigate their egress from the tumor. Combining single-cell transcriptomics and flow cytometry, we found that while a diverse mix of CD8 T cell subsets enter the tumor, all CD8 T cells retained within this environment for more than 72 h developed an exhausted phenotype, revealing the rapid establishment of this program. Rather than forming tumor-resident populations, non-effector subsets, which express TCF-1 and include memory and stem-like cells, were continuously recruited into the tumor, but this recruitment was balanced by concurrent egress to the tumor-draining lymph node. Thus, the TCF-1+ CD8 T cell niche in tumors is highly dynamic, with the circulation of cells between the tumor and peripheral lymphoid tissue to bridge systemic and intratumoral responses.
登录
查看更多内容
通过PD-1-PD-1配体阻滞来振兴耗尽的HIV特异性T细胞。
影响因子：
15.3
作者：
Freeman, Gordon J.;Wherry, E. John;Ahmed, Rafi;Sharpe, Arlene H.
通讯作者：
Sharpe, Arlene H.
DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
影响因子：
11.2
作者：
Harlin H;Meng Y;Peterson AC;Zha Y;Tretiakova M;Slingluff C;McKee M;Gajewski TF
通讯作者：
Gajewski TF
影响因子：
11.2
作者：
Blank, C;Brown, I;Gajewski, TF
通讯作者：
Gajewski, TF
影响因子：
4.4
作者：
Gottschalk, Rachel A.;Corse, Emily;Allison, James P.
通讯作者：
Allison, James P.