The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.
PD-1 marks dysfunctional regulatory T cells in malignant gliomas
Open accessAbstract
Immunotherapies targeting the immune checkpoint receptor programmed cell death protein 1 (PD-1) have shown remarkable efficacy in treating cancer. CD4 + CD25 hi FoxP3 + Tregs are critical regulators of immune responses in autoimmunity and malignancies, but the functional status of human Tregs expressing PD-1 remains unclear. We examined functional and molecular features of PD-1 hi Tregs in healthy subjects and patients with glioblastoma multiforme (GBM), combining functional assays, RNA sequencing, and cytometry by time of flight (CyTOF). In both patients with GBM and healthy subjects, circulating PD-1 hi Tregs displayed reduced suppression of CD4 + effector T cells, production of IFN-γ, and molecular signatures of exhaustion. Transcriptional profiling of tumor-resident Tregs revealed that several genes coexpressed with PD-1 and associated with IFN-γ production and exhaustion as well as enrichment in exhaustion signatures compared with circulating PD-1 hi Tregs. CyTOF analysis of circulating and tumor-infiltrating Tregs from patients with GBM treated with PD-1-blocking antibodies revealed that treatment shifts the profile of circulating Tregs toward a more exhausted phenotype reminiscent of that of tumor-infiltrating Tregs, further increasing IFN-γ production. Thus, high PD-1 expression on human Tregs identifies dysfunctional, exhausted Tregs secreting IFN-γ that exist in healthy individuals and are enriched in tumor infiltrates, possibly losing function as they attempt to modulate the antitumoral immune responses.
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“coinhibitory receptors expressed on T cells — cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) (2, 3) and programmed cell death protein 1 (PD-1) (4, 5).”
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“tions, increased expression of PD-1 on CD8+ T effector cells has been associated with an “exhausted” phenotype, distinguished by progressive loss of effector functions, including proliferation and cytokine production (23).”
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PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression
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Watson, M. J., Vignali, P. D. A., Mullett, S. J., Overacre-Delgoffe, A. E., Peralta, R. M., Grebinoski, S., Menk, A. V., Rittenhouse, N. L., DePeaux, K., Whetstone, R. D., et al. (2021) · Nature · doi:10.1038/s41586-020-03045-2 · Cited by 1,259
Immune checkpoint inhibitors in cancer therapy: a focus on T‐regulatory cells
Sasidharan Nair, V., & Elkord, E. (2018) · Immunology & Cell Biology · doi:10.1111/imcb.1003 · Cited by 298
Collier, J. L., Weiss, S. A., Pauken, K. E., Sen, D. R., & Sharpe, A. H. (2021) · Nature Immunology · doi:10.1038/s41590-021-00949-7 · Cited by 237
TP53 mutations in myelodysplastic syndromes and secondary AML confer an immunosuppressive phenotype
Sallman, D. A., McLemore, A. F., Aldrich, A. L., Komrokji, R. S., McGraw, K. L., Dhawan, A., Geyer, S., Hou, H.-A., Eksioglu, E. A., Sullivan, A., et al. (2020) · Blood · doi:10.1182/blood.2020006158 · Cited by 196
Neuropilin-1: a checkpoint target with unique implications for cancer immunology and immunotherapy
Chuckran, C. A., Liu, C., Bruno, T. C., Workman, C. J., & Vignali, D. A. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-000967 · Cited by 147
Metadata
- Authors
- Lowther, D. E., Goods, B. A., Lucca, L. E., Lerner, B. A., Raddassi, K., van Dijk, D., Hernandez, A. L., Duan, X., Gunel, M., Coric, V., Krishnaswamy, S., Love, J. C., & Hafler, D. A.
- Venue
- JCI Insight
- Published
- 2016-04-21
- Volume
- 1
- Issue
- 5
- ISSN
- 2379-3708 (ISSN-L)
- OpenAlex
- W2338890931
- Cited by
- 253
- References
- 16
- FWCI
- 10.82
- Type
- journal article
- Language
- en
- Open access
- gold
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- Lowther, D. E., Goods, B. A., Lucca, L. E., Lerner, B. A., Raddassi, K., van Dijk, D., Hernandez, A. L., Duan, X., Gunel, M., Coric, V., Krishnaswamy, S., Love, J. C., & Hafler, D. A. (2016). PD-1 marks dysfunctional regulatory T cells in malignant gliomas. JCI Insight. https://doi.org/10.1172/jci.insight.85935
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
