ArticleJournal of experimental & clinical cancer research : CR2021
Combinational blockade of MET and PD-L1 improves pancreatic cancer immunotherapeutic efficacy.
Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 52 citations in OpenAlex.
- Efficacy and safety of multi-target tyrosine kinase inhibitor AL2846 combined with gemcitabine in pancreatic cancer.Investigational new drugs · 2025Trial
- C-MET tyrosine kinase receptor: mechanisms, clinical applications and future perspectives in cancer therapy.Signal transduction and targeted therapy · 2026Review
- MET-associated immune prognostic signature predicts survival and guides personalized therapy in glioma.Acta neuropathologica communications · 2026Article
- Orai1- and STIM1-mediated calcium signaling controls PD-L1 expression and modulates antitumor immunity in oral cancer.The journal of physiological sciences : JPS · 2026Article
- MET pathway inhibition increases chemo-immunotherapy efficacy in small cell lung cancer.Cell reports. Medicine · 2025Article
- MicroRNA-130b Suppresses Malignant Behaviours and Inhibits the Activation of the PI3K/Akt Signaling Pathway by Targeting MET in Pancreatic Cancer.Biochemical genetics · 2025Article
- Circulating Tumor Cells in Head and Neck Squamous-Cell Carcinoma Exhibit Distinct Properties Based on Targeted Epithelial-Related Markers.Current issues in molecular biology · 2025Article
- Targeting HGF/c-MET signaling to regulate the tumor microenvironment: Implications for counteracting tumor immune evasion.Cell communication and signaling : CCS · 2025Review
- Investigating the function and targeting of MET protein as an oncogene kinase in pancreatic ductal adenocarcinoma: A microarray data integration.BioImpacts : BI · 2025Review
- The Clinicopathological and Prognostic Significance of the Expression of PD-L1 and MET Genes in Breast Cancer: Potential Therapeutic Targets.Current cancer drug targets · 2025Article
- Pancreatic cancer subtyping - the keystone of precision treatment.Frontiers in immunology · 2025Review
- First-in-Human Dose-Escalation Study of Fianlimab, an Antilymphocyte Activation Gene-3 Antibody, with Cemiplimab in Patients with Advanced Malignancies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Smad4 regulates TGF-β1-mediated hedgehog activation to promote epithelial-to-mesenchymal transition in pancreatic cancer cells by suppressing Gli1 activity.Computational and structural biotechnology journal · 2024Article
- Identification of Gαi3 as a promising molecular oncotarget of pancreatic cancer.Cell death & disease · 2024Article
- Unveiling the Role of HGF/c-Met Signaling in Non-Small Cell Lung Cancer Tumor Microenvironment.International journal of molecular sciences · 2024Review
- A prognostic binary classifier comprised of five critical mRNAs stratified pancreatic cancer patients following resection.Heliyon · 2024Article
- MET Oncogene Targeting for Cancer Immunotherapy.International journal of molecular sciences · 2024Review
- Gap junction beta-4 accelerates cell cycle progression and metastasis through MET-AKT activation in pancreatic cancer.Cancer science · 2024Article
- EPYC functions as a novel prognostic biomarker for pancreatic cancer.Scientific reports · 2024Article
- Construction and validation of a RARRES3-based prognostic signature related to the specific immune microenvironment of pancreatic cancer.Frontiers in oncology · 2024Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundDysregulated expression and activation of receptor tyrosine kinases (RTKs) are associated with a range of human cancers. However, current RTK-targeting strategies exert little effect on pancreatic cancer, a highly malignant tumor with complex immune microenvironment. Given that immunotherapy for pancreatic cancer still remains challenging, this study aimed to elucidate the prognostic role of RTKs in pancreatic tumors with different immunological backgrounds and investigate their targeting potential in pancreatic cancer immunotherapy.
methodsKaplan-Meier plotter was used to analyze the prognostic significance of each of the all-known RTKs to date in immune "hot" and "cold" pancreatic cancers. Gene Expression Profiling Interactive Analysis-2 was applied to assess the differential expression of RTKs between pancreatic tumors and normal pancreatic tissues, as well as its correlation with immune checkpoints (ICPs). One hundred and fifty in-house clinical tissue specimens of pancreatic cancer were collected for expression and correlation validation via immunohistochemical analysis. Two pancreatic cancer cell lines were used to demonstrate the regulatory effects of RTKs on ICPs by biochemistry and flow cytometry. Two in vivo models bearing pancreatic tumors were jointly applied to investigate the combinational regimen of RTK inhibition and immune checkpoint blockade for pancreatic cancer immunotherapy.
resultsMET was identified as a pancreatic cancer-specific RTK, which is significantly associated with prognosis in both immune "hot" and "cold" pancreatic cancers. MET was observed to be highly upregulated in pancreatic cancer tissues, and positively correlated with PD-L1 levels. Elevated MET and PD-L1 expressions were closely associated with lymph node metastasis, tumor TNM stage, and overall survival in pancreatic cancer. Mechanistically, MET could interact with PD-L1, and maintain its expression level in multiple ways. MET deficiency was found to facilitate lymphocyte infiltration into pancreatic tumors. Finally, significant benefits of combining MET inhibition with PD-1/PD-L1 blockage were verified in both orthotopic and subcutaneous mouse models of pancreatic cancer.
conclusionsThis study systematically investigated the potential effectiveness of a novel pancreatic cancer immunotherapy targeting RTKs, and revealed the function of MET in PD-L1 regulation as well as the combined therapeutic efficacy of MET and PD-L1 in pancreatic cancer.
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