ArticleProceedings of the National Academy of Sciences of the United States of America2019
Reactive oxygen species modulate macrophage immunosuppressive phenotype through the up-regulation of PD-L1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers.
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Who cites it
122 citing papers in PubMed.
- Fasting-Mimicking Diet Is Safe and Reshapes Metabolism and Antitumor Immunity in Patients with Cancer.Cancer discovery · 2022Trial
- NADPH oxidases in immunometabolism and disease pathology: mechanistic networks, pollutant triggers, and therapeutic frontiers.Cellular & molecular immunology · 2026Review
- Regulation of immune checkpoint molecules in cancer immune evasion and therapy.Nature reviews. Cancer · 2026Review
- Bioinspired Artificial Bioenergetic Organelles: Design Principles, Nanofabrication and Therapeutic Translation.Advanced materials (Deerfield Beach, Fla.) · 2026Review
- A Self-Immunoregulatory Nanosensitizer for Sonodynamic Cancer Therapy.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Vascular endothelial growth factor (VEGF) biology and its proposed role in rheumatic diseases pathogenesis.Advances in rheumatology (London, England) · 2026Article
- Reactive Oxygen and Nitrogen Species on Monocyte and Macrophage Biology.Antioxidants (Basel, Switzerland) · 2026Review
- Adaptive therapy for perioperative non-small cell lung cancer: strategies guided by dynamic minimal residual disease adjustment.Translational oncology · 2026Review
- Mitochondrial antioxidant enzyme (SOD2) at the crossroads of redox signaling and cancer progression.Free radical research · 2026Review
- Drug Delivery Systems Repurposing Taxanes as Antitumor Immune Modulators.Biomaterials research · 2026Review
- Nanodynamic Therapy in Colorectal Cancer: Engineering Precision Immunotherapy and Multimodal Synergy.International journal of nanomedicine · 2026Review
- Harnessing human immune system models to validate NADPH oxidase 1 inhibition as treatment for hepatocellular carcinoma.Frontiers in pharmacology · 2026Article
- Comprehensive pan-cancer analysis of p62 reveals its contribution to shaping tumor microenvironment and anti-tumor immunity.Discover oncology · 2025Article
- Cancer-associated fibroblast-derived SOD3 enhances lymphangiogenesis to drive metastasis in lung adenocarcinoma.Angiogenesis · 2025Article
- Combination immunotherapy in hepatocellular carcinoma: synergies among immune checkpoints, TKIs, and chemotherapy.Journal of hematology & oncology · 2025Review
- The role of liver macrophages in viral liver pathogenesis.Journal of leukocyte biology · 2025Review
- Reactive Oxygen Species: From Tumorigenesis to Therapeutic Strategies in Cancer.Cancer medicine · 2025Review
- Cardiovascular Disease and Cancer: A Dangerous Liaison.Arteriosclerosis, thrombosis, and vascular biology · 2025Review
- Targeting Metabolic Vulnerabilities to Combat Drug Resistance in Cancer Therapy.Journal of personalized medicine · 2025Review
- Hypoxia-Induced Reactive Oxygen Species: Their Role in Cancer Resistance and Emerging Therapies to Overcome It.Antioxidants (Basel, Switzerland) · 2025Review
62 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors.
Funding
Abstract
The combination of immune checkpoint blockade with chemotherapy is currently under investigation as a promising strategy for the treatment of triple negative breast cancer (TNBC). Tumor-associated macrophages (TAMs) are the most prominent component of the breast cancer microenvironment because they influence tumor progression and the response to therapies. Here we show that macrophages acquire an immunosuppressive phenotype and increase the expression of programmed death ligand-1 (PD-L1) when treated with reactive oxygen species (ROS) inducers such as the glutathione synthesis inhibitor, buthionine sulphoximine (BSO), and paclitaxel. Mechanistically, these agents cause accumulation of ROS that in turn activate NF-κB signaling to promote PD-L1 transcription and the release of immunosuppressive chemokines. Systemic in vivo administration of paclitaxel promotes PD-L1 accumulation on the surface of TAMS in a mouse model of TNBC, consistent with in vitro results. Combinatorial treatment with paclitaxel and an anti-mouse PD-L1 blocking antibody significantly improved the therapeutic efficacy of paclitaxel by reducing tumor burden and increasing the number of tumor-associated cytotoxic T cells. Our results provide a strong rationale for the use of anti-PD-L1 blockade in the treatment of TNBC patients. Furthermore, interrogation of chemotherapy-induced PD-L1 expression in TAMs is warranted to define appropriate patient selection in the use of PD-L1 blockade.
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