Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK.
J Exp Med. 2022 Jun 6;219(6). doi: 10.1084/jem.20210749. Epub 2022 Apr 26.
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.
提高免疫检查点疗法的疗效将需要更好地了解免疫细胞如何在肿瘤中被招募和维持。在这里，我们使用肿瘤免疫细胞区室的光转化来鉴定新进入的淋巴细胞，确定它们随时间的变化，并研究它们从肿瘤中的流出。结合单细胞转录组学和流式细胞术，我们发现，虽然进入肿瘤的 CD8 T 细胞亚群种类繁多，但在这种环境中停留超过 72 小时的所有 CD8 T 细胞都发展出了衰竭表型，这表明该程序的快速建立。非效应亚群，包括记忆和干细胞样细胞，表达 TCF-1 并包括在内，而非效应亚群并没有形成肿瘤驻留群体，而是不断被招募到肿瘤中，但这种招募被同时向肿瘤引流淋巴结的流出所平衡。因此，肿瘤中的 TCF-1+CD8 T 细胞龛是高度动态的，细胞在肿瘤和外周淋巴组织之间循环，以桥接系统和肿瘤内反应。
