ArticleBritish journal of cancer2019
Met inhibition revokes IFNγ-induction of PD-1 ligands in MET-amplified tumours.
Article in British journal of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 45 citations in OpenAlex.
- MET Overexpression Is Associated with Superior Immunotherapy Benefit in Advanced Non-Small Cell Lung Cancer.Cancers · 2025Article
- Targeting HGF/c-MET signaling to regulate the tumor microenvironment: Implications for counteracting tumor immune evasion.Cell communication and signaling : CCS · 2025Review
- Dual regulation of gastrointestinal tumor progression by the IFN-γ/STAT1 pathway and prospects for targeted therapy.Frontiers in oncology · 2025Review
- Modulation of MHC expression by interferon-gamma and its influence on PBMC-mediated cytotoxicity in canine mast cell tumour cells.Scientific reports · 2024Article
- Exploration of Immune-Modulatory Effects of Amivantamab in Combination with Pembrolizumab in Lung and Head and Neck Squamous Cell Carcinoma.Cancer research communications · 2024Article
- MET Oncogene Targeting for Cancer Immunotherapy.International journal of molecular sciences · 2024Review
- Novel Lymphocyte-Independent Antitumor Activity by PD-1 Blocking Antibody against PD-1+ Chemoresistant Lung Cancer Cells.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Targeting micro-environmental pathways by PROTACs as a therapeutic strategy.Seminars in cancer biology · 2022Review
- Combination strategies with PD-1/PD-L1 blockade: current advances and future directions.Molecular cancer · 2022Review
- Article
- MET overexpression contributes to STAT4-PD-L1 signaling activation associated with tumor-associated, macrophages-mediated immunosuppression in primary glioblastomas.Journal for immunotherapy of cancer · 2021Article
- Combinational blockade of MET and PD-L1 improves pancreatic cancer immunotherapeutic efficacy.Journal of experimental & clinical cancer research : CR · 2021Article
- Correlation between PD-L1 expression andOncotarget · 2021Article
- Has programmed cell death ligand-1Translational lung cancer research · 2021Review
- Review
- Combination of molecularly targeted therapies and immune checkpoint inhibitors in the new era of unresectable hepatocellular carcinoma treatment.Therapeutic advances in medical oncology · 2021Review
- Genomic and clinical characteristics ofJournal of Cancer · 2021Article
- Co-stimulatory and co-inhibitory immune markers in solid tumors withFuture science OA · 2020Article
- HGF-Induced PD-L1 Expression in Head and Neck Cancer: Preclinical and Clinical Findings.International journal of molecular sciences · 2020Article
- The AKT-independent MET-V-ATPase-MTOR axis suppresses liver cancer vaccination.Signal transduction and targeted therapy · 2020Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInterferon-induced expression of programmed cell death ligands (PD-L1/PD-L2) may sustain tumour immune-evasion. Patients featuring MET amplification, a genetic lesion driving transformation, may benefit from anti-MET treatment. We explored if MET-targeted therapy interferes with Interferon-γ modulation of PD-L1/PD-L2 in MET-amplified tumours.
methodsPD-L1/PD-L2 expression and signalling pathways downstream of MET or Interferon-γ were analysed in MET-amplified tumour cell lines and in patient-derived tumour organoids, in basal condition, upon Interferon-γ stimulation, and after anti-MET therapy.
resultsPD-L1 and PD-L2 were upregulated in MET-amplified tumour cells upon Interferon-γ treatment. This induction was impaired by JNJ-605, a selective inhibitor of MET kinase activity, and MvDN30, an antibody inducing MET proteolytic cleavage. We found that activation of JAKs/ STAT1, signal transducers downstream of the Interferon-γ receptor, was neutralised by MET inhibitors. Moreover, JAK2 and MET associated in the same signalling complex depending on MET phosphorylation. Results were confirmed in MET-amplified organoids derived from human colorectal tumours, where JNJ-605 treatment revoked Interferon-γ induced PD-L1 expression.
conclusionsThese data show that in MET-amplified cancers, treatment with MET inhibitors counteracts the induction of PD-1 ligands by Interferon-γ. Thus, therapeutic use of anti-MET drugs may provide additional clinical benefit over and above the intended inhibition of the target oncogene.
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