ArticleOncogene2019
Microenvironmental oxygen pressure orchestrates an anti- and pro-tumoral γδ T cell equilibrium via tumor-derived exosomes.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
127 citing papers in PubMed, 3 syntheses or guidelines pooled it, 174 citations in OpenAlex.
- γδ T cells in oral diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Pooled it
- miRNAs Related to Immune Checkpoint Inhibitor Response: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Extracellular Vesicles in Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders: A Systematic Review.International journal of molecular sciences · 2020Pooled it
- Extracellular Vesicles in Head and Neck Cancer-A Systematic Review.Journal of extracellular biology · 2026Review
- Extracellular vesicles in solid tumors: from tumor ecology to engineered therapeutics.Molecular cancer · 2026Review
- Biomimetic nanovesicles and nanotechnology for oral and maxillofacial diseases.Discover nano · 2026Review
- Harnessing Vδ1Frontiers in immunology · 2026Review
- Review
- Exosomal miRNAs: Key Regulators of the Tumor Microenvironment and Cancer Stem Cells.International journal of molecular sciences · 2025Review
- Extracellular vesicles: biogenesis mechanism and impacts on tumor immune microenvironment.Journal of biomedical science · 2025Review
- Interplay between innate-like T-cells and microRNAs in cancer immunity.Discover oncology · 2025Review
- Mechanisms and Functions of γδ T Cells in Tumor Cell Recognition.Current oncology (Toronto, Ont.) · 2025Review
- Exosome-based approaches in cancer along with unlocking new insights into regeneration of cancer-prone tissues.Regenerative therapy · 2025Review
- Pathways and outputs orchestrated in tumor microenvironment cells by hypoxia-induced tumor-derived exosomes in pan-cancer.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Emerging roles of non-coding RNA derived from extracellular vesicles in regulating PD-1/PD-L1 pathway: insights into cancer immunotherapy and clinical applications.Cancer cell international · 2025Review
- A strategy for synergistic enhancement of immune circulation in head and neck squamous cell carcinoma by novel nucleic acid drug therapy and immunotherapy.Journal of translational medicine · 2025Review
- Effect of Extracellular Vesicles Derived From Tumor Cells on Immune Evasion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Article
- Acidity and hypoxia of tumor microenvironment, a positive interplay in extracellular vesicle release by tumor cells.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Article
67 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
γδ T cells are a unique lymphocyte population that have been reported to have either anti- or pro-tumoral functions in several cancer types, but the mechanisms are underinvestigated. Exosomes, initially considered to be cellular "garbage dumpsters," are now implicated in mediating interactions with the cellular environment. Hypoxia is a common feature of solid tumors and is believed to alter tumor-derived exosomes (TEXs), which mediate the hypoxic evolution of the tumor microenvironment in return. This study sought to investigate whether TEXs mediate the anti- and pro-tumoral equilibrium of γδ T cells under different oxygen pressures in the tumor microenvironment. We show that TEXs can alter the expansion and cytotoxicity of γδ T cells in an HSP70-dependent but dendritic cell-independent manner. The stimulating effects of normoxic TEXs on γδ T-cell activity were absent from hypoxic TEXs, which enhanced the suppressive effect of myeloid-derived suppressor cells (MDSCs) on γδ T cells through a miR-21/PTEN/PD-L1 regulation axis. Finally, the therapeutic outcome benefited from combined miR-21 and PD-L1 targeting in oral squamous cell carcinoma (OSCC)-bearing immunocompetent mice. We conclude that oxygen pressure in the tumor microenvironment orchestrates an anti- and pro-tumoral γδ T-cell equilibrium by altering TEX content, which subsequently regulates MDSC function in a miR-21/PTEN/PD-L1-axis-dependent manner. Our results should prompt further investigation into integrated exosomal miRNA inhibition and immune checkpoint inhibitor therapeutic modalities for patients with OSCC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.