ArticleJCI insight2021
PD-L1 tumor-intrinsic signaling and its therapeutic implication in triple-negative breast cancer.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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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.
The trial behind it
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
60 citing papers in PubMed, 83 citations in OpenAlex.
- Review
- High-Dose Sunitinib Accelerates Triple-Negative Breast Cancer Metastasis by Modulating an Immunosuppressive Microenvironment: A Preclinical 4T1 Model Study.Pharmaceutical research · 2026Article
- Tumor-Intrinsic PD-L1 Promotes Breast Cancer Proliferation Through Livin and Galectin-1-Mediated Regulation of SKP2 Expression.International journal of molecular sciences · 2026Article
- Emerging Protein Targets in Triple-Negative Breast Cancer: Beyond Conventional Therapy.Cancers · 2026Review
- Reciprocal regulation of hMENA and TGF-β signaling in cancer-associated fibroblasts promotes EMT, immunosuppression, poor prognosis, and ICT resistance in NSCLC.Journal for immunotherapy of cancer · 2026Article
- Depletion of Soluble PD-L1 with Engineered Nanoparticles Promotes Antitumor Immunity and Tumor Control.International journal of nanomedicine · 2026Article
- Directed evolution-driven reprogramming of PD-L1 for compact and tunable checkpoint modulation.Journal of biological engineering · 2025Article
- Targeting PD-L1-CMTM6 interactions in myeloid cells triggers PD-L1 degradation and enhances cytotoxic T-cell expansion.Journal for immunotherapy of cancer · 2025Article
- PD-L1 regulates c-MET phosphorylation and contributes to MET-dependent resistance to osimertinib in EGFR-mutant NSCLC.Journal of biomedical science · 2025Article
- The Role of Tumor Microenvironment in Triple-Negative Breast Cancer and Its Therapeutic Targeting.Cells · 2025Review
- A novel CD44-targeting aptamer recognizes chemoresistant mesenchymal stem-like TNBC cells and inhibits tumor growth.Bioactive materials · 2025Article
- Impact of the PD-1/PD-L1 inhibitor SCL-1 on MDA-MB231 tumor growth in a humanized MHC-double knockout NOG mouse model.Scientific reports · 2025Article
- Cytoplasmic HMGB1 promotes the activation of JAK2-STAT3 signaling and PD-L1 expression in breast cancer.Molecular medicine (Cambridge, Mass.) · 2025Article
- Programmed Death-1 Ligand 1 Domain Organization, Signaling Motifs, and Interactors in Cancer Immunotherapy.Cancers · 2025Review
- TIM-3 teams up with PD-1 in cancer immunotherapy: mechanisms and perspectives.Molecular biomedicine · 2025Review
- Cell-intrinsic PD-L1 signaling drives immunosuppression by myeloid-derived suppressor cells through IL-6/Jak/Stat3 in PD-L1-high lung cancer.Journal for immunotherapy of cancer · 2025Article
- Therapeutic Applications of Programmed Death Ligand 1 Inhibitors in Small Cell Lung Cancer.Biomedicines · 2025Review
- Article
- PD-L1/ITGB4 Axis Modulates Sensitivity of Hepatocellular Carcinoma to Sorafenib via FAK/AKT/mTOR Signaling Pathway.ImmunoTargets and therapy · 2025Article
- The Tumor Immune Environment: Advances in the Cancer Immunotherapy Era.Methods in molecular biology (Clifton, N.J.) · 2025Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Although the immune checkpoint role of programmed death ligand 1 (PD-L1) has been established and targeted in cancer immunotherapy, the tumor-intrinsic role of PD-L1 is less appreciated in tumor biology and therapeutics development, partly because of the incomplete mechanistic understanding. Here we demonstrate a potentially novel mechanism by which PD-L1 promotes the epithelial-mesenchymal transition (EMT) in triple-negative breast cancer (TNBC) cells by suppressing the destruction of the EMT transcription factor Snail. PD-L1 directly binds to and inhibits the tyrosine phosphatase PTP1B, thus preserving p38-MAPK activity that phosphorylates and inhibits glycogen synthase kinase 3β (GSK3β). Via this mechanism, PD-L1 prevents the GSK3β-mediated phosphorylation, ubiquitination, and degradation of Snail and consequently promotes the EMT and metastatic potential of TNBC. Significantly, PD-L1 antibodies that confine the tumor-intrinsic PD-L1/Snail pathway restricted TNBC progression in immunodeficient mice. More importantly, targeting both tumor-intrinsic and tumor-extrinsic functions of PD-L1 showed strong synergistic tumor suppression effect in an immunocompetent TNBC mouse model. Our findings support that PD-L1 intrinsically facilitates TNBC progression by promoting the EMT, and this potentially novel PD-L1 signaling pathway could be targeted for better clinical management of PD-L1-overexpressing TNBCs.
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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.