ArticleJournal of translational medicine2023
Immunization with a multi-antigen targeted DNA vaccine eliminates chemoresistant pancreatic cancer by disrupting tumor-stromal cell crosstalk.
Article in Journal of translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- DNA-based vaccines: Advances, applications, and future prospects.Genes & diseases · 2026Review
- Unravelling the pathogenesis and therapeutic approaches of pancreatic ductal adenocarcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Osteocyte-Derived GDF15 Promotes Paclitaxel Resistance, Tumor Growth, and Bone Microenvironment Regulation in Prostate Cancer.Current issues in molecular biology · 2026Article
- Tailoring Vascular-Immune Homeostasis via Manganese-DNA Complex-Armed Immunogenic Extracellular Vesicles for Pancreatic Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Next-generation neoantigen mRNA vaccines: Immuno-engineering strategies for precision cancer immunotherapy.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Harnessing Tumor Organoids to Revolutionize Immunotherapy Research.Cancer medicine · 2026Review
- Comprehensive analysis of MAGE-A10 in pan-cancer and its validation in gastric cancer.Scientific reports · 2025Article
- Organoid models in oncology: advancing precision cancer therapy and vaccine development.Cancer biology & medicine · 2025Review
- Recent Advances in the Development and Efficacy of Anti-Cancer Vaccines-A Narrative Review.Vaccines · 2025Review
- Looking Beyond Checkpoint Inhibitor Monotherapy: Uncovering New Frontiers for Pancreatic Cancer Immunotherapy.Molecular cancer therapeutics · 2025Review
- Therapeutic cancer vaccines in pancreatic cancer.Frontiers in immunology · 2025Review
- Pericytes Modulate Third-Generation Tyrosine Kinase Inhibitor Sensitivity in EGFR-Mutated Lung Cancer Cells Through IL32-β5-Integrin Paracrine Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Mitochondrial DNA-boosted dendritic cell-based nanovaccination triggers antitumor immunity in lung and pancreatic cancers.Cell reports. Medicine · 2024Article
- Review
- Frontiers and future of immunotherapy for pancreatic cancer: from molecular mechanisms to clinical application.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPancreatic ductal adenocarcinoma (PDAC) is characterised by limited responses to chemoimmunotherapy attributed to highly desmoplastic tumor microenvironment. Disrupting the tumor-stromal cell crosstalk is considered as an improved PDAC treatment strategy, whereas little progress has been made due to poor understanding of its underlying mechanism. Here, we examined the cellular role of melanoma associated antigen A isoforms (MAGEA) in regulating tumor-stromal crosstalk mediated chemoresistance.
methodsWe used clinical samples to explore the correlation between MAGEA expression and patient prognosis in multiple cancers. We utilized cancer cell lines, patient derived organoids and orthotopic PDAC model to examine the function of MAGEA in chemoresistance. We performed biochemical, proteome profiler array and transcriptional analysis to uncover a mechanism that governs tumor-stromal crosstalk. We developed a multi-MAGEA antigen targeted DNA vaccine and tested its effect on PDAC tumor growth.
resultsWe establish MAGEA as a regulator of the tumor-stromal crosstalk in PDAC. We provide strong clinical evidence indicating that high MAGEA expression, including MAGEA2, MAGEA3 and MAGEA10, correlates with worse chemotherapeutic response and poor prognosis in multiple cancers, while their expression is up-regulated in chemoresistant PDAC patient derived organoids and cancer cell lines. Mechanistically, MAGEA2 prohibits gemcitabine-induced JNK-c-Jun-p53 mediated cancer cell apoptosis, while gemcitabine stimulated pancreatic stellate cells secretes GDF15 to further enhance the gemcitabine resistance of MAGEA2 expressing cells by activating GFRAL-RET mediated Akt and ERK1/2 dependent survival pathway. Strikingly, immunization with a DNA vaccine that targeting multiple MAGEA antigens, including MAGEA2, MAGEA3 and MAGEA10, elicits robust immune responses against the growth of gemcitabine resistant tumors.
conclusionsThese findings suggest that targeting MAGEA-mediated paracrine regulation of chemoresistance by immunotherapy can be an improved pancreatic cancer treatment strategy.
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