COX2/mPGES1/PGE 2 pathway regulates PD-L1 expression in tumor-associated macrophages and myeloid-derived suppressor cells
Open accessAbstract
Significance Programmed cell death protein ligand 1 (PD-L1)–expressing cells mediate tumor evasion from immune system by suppressing activated T lymphocytes. A bioactive lipid prostaglandin E 2 (PGE 2 ) formed from arachidonic acid by COXs and PGE 2 synthases (PGESs) facilitates both cancer inflammation and immune suppression. Here, we show that tumor cells can induce PD-L1 expression in bone marrow–derived cells by affecting PGE 2 metabolism in hematopoietic cells. The tumor-induced PD-L1 expression was limited to the myeloid cell lineage and, specifically, to the macrophages and myeloid-derived suppressor cells. Collectively, the obtained results demonstrate that selective inhibition of PGE 2 -forming enzymes COX2, murine PGES1, or genetic overexpression of PGE 2 -degrading enzyme 15-hydroxyprostaglandin dehydrogenase could provide a novel approach to regulate both PGE 2 levels and PD-L1 expression in cancer, thus alleviating the immune suppression and stimulating antitumor immune response.
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Radiotherapy stimulates PD-L1 upregulation on cells in the myeloid compartment.
“stimulate the upregulation of PD-L1 on cells from the myeloid compartment”
From Immunomodulation by targeted anticancer agents (2021) · cites this paper as Prima et al., 2017
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- Authors
- Prima, V., Kaliberova, L. N., Kaliberov, S., Curiel, D. T., & Kusmartsev, S.
- Affiliations
- University of Florida (US)
- Washington University in St. Louis (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2017-01-17
- Volume
- 114
- Issue
- 5
- Pages
- 1117-1122
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5293015
- OpenAlex
- W2577696913
- Cited by
- 494
- References
- 33
- Citations by year
- 2026: 32 · 2025: 55 · 2024: 40 · 2023: 77 · 2022: 65 · 2021: 60 · 2020: 69 · 2019: 46 · 2018: 31 · 2017: 17 · 2016: 1
- FWCI
- 20.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- James and Esther King Biomedical Research Program (10KN-10)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- PD-L1 expression, prostaglandin E2, cyclooxygenase-2, 15-hydroxyprostaglandin dehydrogenase, tumor-associated macrophages, myeloid-derived suppressor cells, tumor immune evasion, bone marrow-derived cells, arachidonic acid metabolism, antitumor immunity, tumor inflammation
- MeSH terms
- Prostaglandin-E Synthases, Myeloid-Derived Suppressor Cells, Animals, Urinary Bladder Neoplasms, Bone Marrow Cells, Cell Communication, Humans, Hydroxyprostaglandin Dehydrogenases, Macrophages, Mice, Inbred C3H, Prostaglandin Antagonists, Dinoprostone, Gene Expression Regulation, Neoplastic, Mice, SCID, Mice, Inbred NOD, Coculture Techniques, Cell Line, Tumor, Mice, Cyclooxygenase 2, B7-H1 Antigen, Heterografts
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