PD-1 receptor deficiency enhances CD30+ Treg cell function in melanoma
Regulatory T (T<sub>reg</sub>) cells are vital for immune suppression. The role of the coreceptor programmed cell death 1 receptor (PD-1) in T<sub>reg</sub> cell function is controversial. Here, we demonstrate that PD-1 deficiency enhances the function of T<sub>reg</sub> cells through expression of a compensatory network of coinhibitory receptors. CD30 has a central role within this network, driving the T<sub>reg</sub> cell suppressive function within the tumor microenvironment. Mechanistically, PD-1 deficiency enhances STAT5 signaling in T<sub>reg</sub> cells, which induces CD30 expression. These data indicate a role for PD-1 as a checkpoint that negatively controls CD30 expression in T<sub>reg</sub> cells to limit their suppressive function. Understanding the functional changes that PD-1 has on T<sub>reg</sub> cells might enable combination therapies with better treatment outcomes in cancer.
Authors
- Jing Xuan Lim (ORCID: https://orcid.org/0000-0003-2288-3812)
- Graham Anderson (ORCID: https://orcid.org/0000-0002-2917-4085)
- Stephanie Laba (ORCID: https://orcid.org/0000-0001-6120-2691)
- Jérémie Nsengimana (ORCID: https://orcid.org/0000-0002-3603-4208)
- Yin‐Shan Ng (ORCID: https://orcid.org/0000-0002-4982-1999)
- Arian Laurence (ORCID: https://orcid.org/0000-0003-0942-8292)
- Shoba Amarnath (ORCID: https://orcid.org/0000-0001-8081-8432)
- Hong‐Wei Sun (ORCID: https://orcid.org/0000-0001-9765-6505)
- Katie J Smith (ORCID: https://orcid.org/0000-0003-1034-1629)
- Tegan McTaggart
- Jonathan Coxhead (ORCID: https://orcid.org/0000-0002-6128-9560)
- Ioana Cosgarea (ORCID: https://orcid.org/0000-0002-2639-6264)
- Catherine Arden (ORCID: https://orcid.org/0000-0002-3642-3182)
- Penny E. Lovat (ORCID: https://orcid.org/0000-0002-6657-6825)
- Rafiqul Hussain (ORCID: https://orcid.org/0000-0002-1436-8944)
- Gillian Hulme (ORCID: https://orcid.org/0000-0001-8371-2780)
- Amelia Williams
- Seol Kyoung Jung
Institutions
- Nuffield Orthopaedic Centre (GB)
- University of Oxford (GB)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (US)
- NIHR Newcastle Biomedical Research Centre (GB)
- Oxford BioMedica (United Kingdom) (GB)
- University of Birmingham (GB)
- Newcastle University (GB)
Publication Details
- Journal
- Nature Immunology
- Published
- 2025-06-02
- DOI
- https://doi.org/10.1038/s41590-025-02172-0
- Citations
- 16
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 12.76
Funders
- Pfizer
- Seagen
- National Institute for Health and Care Research
- Academy of Medical Sciences
- University of Exeter
- Newcastle University
- Newcastle upon Tyne Hospitals NHS Foundation Trust
- LEO Pharma Research Foundation
- National Centre for the Replacement Refinement and Reduction of Animals in Research
- LEO Fondet
- National Institutes of Health
- Medical Research Council
- NIHR Newcastle Biomedical Research Centre
- National Institute of Arthritis and Musculoskeletal and Skin Diseases