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标题：PD-1-stimulated T cell subsets are transcriptionally and functionally distinct
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作者：Shalom Lerrer ; Anna S. Tocheva ; Shoiab Bukhari 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：9
页码：1-18
DOI：10.1016/j.isci.2021.103020
语种：English
出版社：Elsevier
摘要：SummaryDespite the obvious inhibitory outcome of PD-1 signaling, an additional series of functions are activated. We have observed that T cells stimulated through the T cell receptor (TCR) and PD-1 primarily do not proliferate; however, there is a population of cells that proliferates more than through TCR stimulation alone. In this study, we performed flow cytometry and RNA sequencing on individual populations of T cells and discovered that unlike naive T cells, which were inhibited following PD-1 ligation, T cells that proliferated more following PD-1 ligation were associated with effector and central memory phenotypes. We showed that these populations had different gene expression profiles following PD-1 ligation with PD-L1 compared to PD-L2. The presence of transcriptionally and functionally distinct T cell populations responsive to PD-1 ligation provides new insights into the biology of PD-1 and suggest the use of T cell subset-specific approaches to improve the clinical outcome of PD-1 blockade.Graphical abstractDisplay OmittedHighlights•Most of the genes induced or regulated by PD-1 are T cell subsets specific•PD-1 ligation with PD-L1 or PD-L2 results in diverged transcriptomic signatures•PD-1-induced STAT1 upregulation correlates with responses to checkpoint blockadeImmunology; Cancer; Transcriptomics