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Lookup NU author(s): Dr Jing Xuan LimORCiD, Tegan McTaggart, Dr Katie SmithORCiD, Dr Gill HulmeORCiD, Dr Stephanie Laba, Dr Yi NgORCiD, Dr Amelia Williams, Raf Hussain, Dr Jonathan Coxhead, Dr Ioana Cosgarea, Dr Catherine ArdenORCiD, Dr Jérémie NsengimanaORCiD, Professor Penny LovatORCiD, Dr Shoba AmarnathORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2025.Regulatory T (Treg) cells are vital for immune suppression. The role of the coreceptor programmed cell death 1 receptor (PD-1) in Treg cell function is controversial. Here, we demonstrate that PD-1 deficiency enhances the function of Treg cells through expression of a compensatory network of coinhibitory receptors. CD30 has a central role within this network, driving the Treg cell suppressive function within the tumor microenvironment. Mechanistically, PD-1 deficiency enhances STAT5 signaling in Treg cells, which induces CD30 expression. These data indicate a role for PD-1 as a checkpoint that negatively controls CD30 expression in Treg cells to limit their suppressive function. Understanding the functional changes that PD-1 has on Treg cells might enable combination therapies with better treatment outcomes in cancer.
Author(s): Lim JX, McTaggart T, Jung SK, Smith KJ, Hulme G, Laba S, Ng YQ, Williams A, Hussain R, Coxhead J, Cosgarea I, Arden C, Nsengimana J, Lovat P, Anderson G, Sun H-W, Laurence A, Amarnath S
Publication type: Article
Publication status: Published
Journal: Nature Immunology
Year: 2025
Pages: epub ahead of print
Online publication date: 02/06/2025
Acceptance date: 25/04/2025
Date deposited: 16/06/2025
ISSN (print): 1529-2908
ISSN (electronic): 1529-2916
Publisher: Nature Research
URL: https://doi.org/10.1038/s41590-025-02172-0
DOI: 10.1038/s41590-025-02172-0
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