ArticleJournal of experimental & clinical cancer research : CR2022
Reactive oxygen species reprogram macrophages to suppress antitumor immune response through the exosomal miR-155-5p/PD-L1 pathway.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.
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Who cites it
68 citing papers in PubMed, 1 synthesis or guideline pooled it, 95 citations in OpenAlex.
- Role of miR-155 in inflammatory autoimmune diseases: a comprehensive review.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Pooled it
- Circulating MicroRNAs in non-small cell lung cancer: Clinical potential, analytic pitfalls, and barriers to implementation.The journal of liquid biopsy · 2026Review
- Potential Role of Exosomes in the Pathogenesis, Diagnosis, and Treatment of Ovarian Cancer.Cancers · 2026Review
- miR-181a-5p of MSCs-derived exosomes promote vascular formation and cell proliferation by PTEN/PI3K/AKT axis in HUVECs.Scientific reports · 2026Article
- Exosomes in Ovarian Cancer: Promoters, Biomarkers, and Therapeutic Targets.International journal of nanomedicine · 2026Review
- MicroRNA-targeted reprogramming of CD8+ T cells against cancer.Frontiers in immunology · 2026Review
- HBx hijacks the miR-19a-3p/BAMBI/TGF-β1 axis to impair the anti-tumour activity of CD4Clinical and translational medicine · 2026Article
- Tumor microenvironment-activated ROS enhancers for effective inhibition of osteosarcoma.BMC biotechnology · 2025Article
- A Novel Function of Glycerol Kinase Alleviates LPS-Induced Inflammatory Responses by the p38/STAT3 Pathway and Mitigates ROS Generation in Kupffer Cells.Antioxidants (Basel, Switzerland) · 2025Article
- Unveiling the role of TAM-derived extracellular vesicles in glioma progression through Treg polarization and immune suppression.Oncogene · 2025Article
- Oxidative stress in cancer: from tumor and microenvironment remodeling to therapeutic frontiers.Molecular cancer · 2025Review
- Construction of mitochondrial signature (MS) for the prognosis of ovarian cancer.Discover oncology · 2025Article
- The role of exosomal PD-L1 in NSCLC immunotherapy.Immunotherapy · 2025Review
- Unraveling the advances of non-coding RNAs on the tumor microenvironment: innovative strategies for cancer therapies.Journal of translational medicine · 2025Review
- Exosomal PD-L1 derived from hypoxia nasopharyngeal carcinoma cell exacerbates CD8Cancer immunology, immunotherapy : CII · 2025Article
- 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
- Targeting Redox Signaling Through Exosomal MicroRNA: Insights into Tumor Microenvironment and Precision Oncology.Antioxidants (Basel, Switzerland) · 2025Review
- Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets.Signal transduction and targeted therapy · 2025Review
- Exosomal integrin alpha 3 promotes epithelial ovarian cancer cell migration via the S100A7/p-ERK signaling pathway.Acta biochimica et biophysica Sinica · 2025Article
- Orchestration of Tumor-Associated Macrophages in the Tumor Cell-Macrophage-CD8International journal of biological sciences · 2025Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundCancer cells have an imbalance in oxidation-reduction (redox) homeostasis. Understanding the precise mechanisms and the impact of the altered redox microenvironment on the immunologic reaction to tumors is limited.
methodsWe isolated exosomes from ovarian cancer cells through ultracentrifuge and characterized by Western-blots and Nanoparticle Tracking Analysis. 2D, 3D-coculture tumor model, and 3D live cell imaging were used to study the interactions between tumor cells, macrophages and CD3 T cells in vitro. The role of exosomal miR-155-5p in tumor growth was evaluated in xenograft nude mice models and immune-competent mice models. Flow cytometry and flow sorting were used to determine the expression levels of miR-155-5p and PD-L1 in ascites and splenic macrophages, and the percentages of CD3 T cells subpopulations.
resultsThe elevation of reactive oxygen species (ROS) greatly downregulated exosomal miR-155-5p expression in tumor cells. Neutralization of ROS with N-acetyl-L-cysteine (NAC) increased the levels of miR-155-5p in tumor exosomes that were taken up by macrophages, leading to reduction of macrophage migration and tumor spheroid infiltration. We further found that programmed death ligand 1 (PD-L1) is a functional target of miR-155-5p. Co-culture of macrophages pre-treated with NAC-derived tumor exosomes or exosomal miR-155-5p with T-lymphocytes leading to an increased percentage of CD8
conclusionsOur findings demonstrate a novel mechanism, ROS-induced down-regulation of miR-155-5p, by which tumors modulate the microenvironment that favors tumor growth. Understanding of the negative impact of ROS on the tumor immune response will improve current therapeutic strategies. Targeting miR-155-5p can be an alternative approach to prevent formation of an immunosuppressive TME through downregulation of PD-L1 and other immunosuppressive factors.
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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.