ArticleThe Journal of clinical investigation2019
Breaking barriers for T cells by targeting the EPHA2/TGF-β/COX-2 axis in pancreatic cancer.
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 14 papers.
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Who cites it
14 citing papers in PubMed, 15 citations in OpenAlex.
- Acquired resistance to immunotherapy by physical barriers with cancer cell-expressing collagens in non-small cell lung cancer.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Erythropoietin-induced hepatocyte receptor A2 regulates effect of pyroptosis on gastrointestinal colorectal cancer occurrence and metastasis resistance.World journal of gastrointestinal oncology · 2024Review
- Targeting inflammation as cancer therapy.Journal of hematology & oncology · 2024Review
- Article
- The impact of lipids on the cancer-immunity cycle and strategies for modulating lipid metabolism to improve cancer immunotherapy.Acta pharmaceutica Sinica. B · 2023Review
- The EPH/Ephrin System in Pancreatic Ductal Adenocarcinoma (PDAC): From Pathogenesis to Treatment.International journal of molecular sciences · 2023Review
- LRRC8A Is a Promising Prognostic Biomarker and Therapeutic Target for Pancreatic Adenocarcinoma.Cancers · 2022Article
- Implications of the Essential Role of Small Molecule Ligand Binding Pockets in Protein-Protein Interactions.The journal of physical chemistry. B · 2022Article
- LRG1 in pancreatic cancer cells promotes inflammatory factor synthesis and the angiogenesis of HUVECs by activating VEGFR signaling.Journal of gastrointestinal oncology · 2022Article
- Interplay between cyclooxygenase‑2 and microRNAs in cancer (Review).Molecular medicine reports · 2021Article
- MicroRNA-497-5p Is Downregulated in Hepatocellular Carcinoma and Associated with Tumorigenesis and Poor Prognosis in Patients.International journal of genomics · 2021Article
- Cyclooxygenase-2 Inhibitor: A Potential Combination Strategy With Immunotherapy in Cancer.Frontiers in oncology · 2021Review
- EPHA mutation as a predictor of immunotherapeutic efficacy in lung adenocarcinoma.Journal for immunotherapy of cancer · 2020Article
- Long Noncoding RNA OIP5-AS1 Promotes the Progression of Liver Hepatocellular Carcinoma via Regulating the hsa-miR-26a-3p/EPHA2 Axis.Molecular therapy. Nucleic acids · 2020Article
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Abstract
Pancreatic ductal adenocarcinoma is projected to become the second leading cause of cancer-related death and is largely resistant to immunotherapies. The tumor microenvironment, largely composed of heterogeneous myeloid cells, creates a physical, metabolic, and immunosuppressive barrier that prevents T cells from infiltrating cancer beds. In this issue of the JCI, Markosyan and colleagues have reported a tumor-intrinsic mechanism that excludes T cells from the vicinity of tumor cells. They showed that a receptor tyrosine kinase, ephrin-A receptor 2 (EPHA2), regulates prostaglandin endoperoxide synthase 2 (PTGS2) (encodes COX-2) expression in a TGF-β signaling-dependent manner. Genetic ablation of Epha2 or Ptgs2 in preclinical models or pharmacological inhibition of COX-2 elicited the transformation of this immunosuppressive microenvironment into a T cell-permissive milieu. Consequent T cell relocation rendered this immunoresistant malignancy responsive to combinations of checkpoint blockers and CD40 agonists. Because the association between T cell infiltration and the EPHA2/TGF-β/COX-2 axis is supported by independent clinical data, these results provide a rationale for ensuing clinical trials aimed at incorporating pancreatic cancer into the range of immunotherapy-responsive tumors.
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