ArticleThe Journal of clinical investigation2019
Tumor cell-intrinsic EPHA2 suppresses anti-tumor immunity by regulating PTGS2 (COX-2).
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers.
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Who cites it
115 citing papers in PubMed, 165 citations in OpenAlex.
- Research progress of aptamers in the diagnosis and treatment of colorectal cancer (Review).Molecular medicine reports · 2026Review
- EPHA2/CD44-directed trafficking enhances endosomal leakiness and antisense therapy delivery.The Journal of cell biology · 2026Article
- Blockade of Tumor TAK1 Induces DNA Damage and Immunogenic cGAS-STING Pathway Activation in Pancreatic Cancer.Gastroenterology · 2026Article
- Inhibiting CXCR2 Remodels the Tumor Microenvironment and Blunts Tumor Progression and Dissemination of High-Grade Serous Carcinoma.Cancer research communications · 2026Article
- An Injectable Metal-Drug Supramolecular Condensate Enables Radiosensitization and Systemic Antitumor Immunity for Post-Surgical Osteosarcoma Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- IFI30 reprograms glioblastoma-associated macrophage and induces immune evasion by MAFF/PTGS2 pathway.Acta pharmaceutica Sinica. B · 2026Article
- Antitumor Activities of Chimeric Anti-EphA2 Antibodies in Xenograft Models of Breast, Pancreatic, and Colorectal Cancers.International journal of molecular sciences · 2026Article
- Tumor Lipidomic Changes after Treatment with Polymeric Hydroxychloroquine in a Syngeneic Murine Model of Pancreatic Cancer.ACS omega · 2026Article
- Mapping kinase-dependent tumor immune adaptation with multiplexed single-cell CRISPR screens.bioRxiv : the preprint server for biology · 2026Article
- Current and Future Landscape of Hepatocellular Carcinoma Treatment.Oncology research · 2026Review
- Cyclooxygenases in pancreatic ductal adenocarcinoma: are they inflammatory catalysts for tumor growth.Frontiers in oncology · 2026Review
- Preclinical Evaluation of an Anti-EphA2 Minibody-Based ImmunoPET Agent as a Diagnostic Tool For Cancer.Molecular imaging and biology · 2025Article
- Unveiling prognostic biomarkers and immunotherapeutic insights in prostate cancer through multi-omics and machine learning.European journal of medical research · 2025Article
- Targeting tumor-intrinsic TAK1 triggers anti-tumor immunity and sensitizes pancreatic cancer to checkpoint blockade.bioRxiv : the preprint server for biology · 2025Article
- Network toxicology and molecular docking elucidate the hepatotoxic and carcinogenic mechanisms of potassium sorbate validated by in vitro assays.Scientific reports · 2025Article
- Article
- Activated T Cells Break Tumor Immunosuppression by Macrophage Reeducation.Cancer discovery · 2025Article
- GOT2: New therapeutic target in pancreatic cancer.Genes & diseases · 2025Review
- Developing and Characterizing the Tumor-Targeting Efficiency of an Anti-EphA2-CD11b Bispecific Antibody.Bioconjugate chemistry · 2025Article
- Curcumin alleviates LPS-induced WI-38 cell inflammation injury by regulating PTGS2 expression.Hereditas · 2025Article
55 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
Resistance to immunotherapy is one of the biggest problems of current oncotherapeutics. WhileT cell abundance is essential for tumor responsiveness to immunotherapy, factors that define the T cell inflamed tumor microenvironment are not fully understood. We conducted an unbiased approach to identify tumor-intrinsic mechanisms shaping the immune tumor microenvironment(TME), focusing on pancreatic adenocarcinoma because it is refractory to immunotherapy and excludes T cells from the TME. From human tumors, we identified EPHA2 as a candidate tumor intrinsic driver of immunosuppression. Epha2 deletion reversed T cell exclusion and sensitized tumors to immunotherapy. We found that PTGS2, the gene encoding cyclooxygenase-2, lies downstream of EPHA2 signaling through TGFβ and is associated with poor patient survival. Ptgs2 deletion reversed T cell exclusion and sensitized tumors to immunotherapy; pharmacological inhibition of PTGS2 was similarly effective. Thus, EPHA2-PTGS2 signaling in tumor cells regulates tumor immune phenotypes; blockade may represent a novel therapeutic avenue for immunotherapy-refractory cancers. Our findings warrant clinical trials testing the effectiveness of therapies combining EPHA2-TGFβ-PTGS2 pathway inhibitors with anti-tumor immunotherapy, and may change the treatment of notoriously therapy-resistant pancreatic adenocarcinoma.
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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.