ArticleGut2014
Targeted depletion of an MDSC subset unmasks pancreatic ductal adenocarcinoma to adaptive immunity.
Article in Gut, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 228 papers, 1 of them a synthesis that pooled it.
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Who cites it
228 citing papers in PubMed, 1 synthesis or guideline pooled it, 320 citations in OpenAlex.
- Immune checkpoint inhibition for pancreatic ductal adenocarcinoma: limitations and prospects: a systematic review.Cell communication and signaling : CCS · 2021Pooled it
- Trial
- Decoding spatiotemporal fibrotic and cellular immunosuppression of therapeutic T cells in live pancreatic ductal adenocarcinoma.Molecular systems biology · 2026Article
- Review
- PGK1 epigenetically silences STING via DNMT1 and its knockdown synergizes with STING agonists in pancreatic cancer.Acta pharmacologica Sinica · 2026Article
- Antibody subclass deficiency accelerates tumorigenesis in genetically engineered mouse models of pancreatic cancer.JCI insight · 2026Article
- GFER Represents a Target for Dual Disruption of Redox Homeostasis and Reactivation of the Immune Response in Pancreatic Adenocarcinoma.Cancer research · 2026Article
- CD300ld blockade overcomes PMN-MDSC-mediated vaccine resistance in advanced tumors.Journal for immunotherapy of cancer · 2026Article
- The effect of CD40 agonist antibody therapy on the pancreatic cancer microenvironment.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- MicroRNA-based strategies to overcome the immunotherapy barrier in pancreatic ductal adenocarcinoma.Frontiers in immunology · 2026Review
- Engineering strategies to address immune and delivery barriers in pancreatic ductal adenocarcinoma: a barrier-matched translational framework.Frontiers in immunology · 2026Review
- Bibliometric analysis of global research trends in pancreatic cancer immunotherapy.Human vaccines & immunotherapeutics · 2025Article
- Irreversible electroporation with intratumoral plant virus immunotherapy induces systemic immunity in a metastatic model of pancreatic cancer.Cancer letters · 2025Article
- The pancreatic tumor microenvironment of treatment-naïve patients causes a functional shift in γδ T cells, impairing their anti-tumoral defense.Oncoimmunology · 2025Article
- The tumour microenvironment in pancreatic cancer - new clinical challenges, but more opportunities.Nature reviews. Clinical oncology · 2025Review
- Extracellular matrix architecture promotes immunosuppressive microenvironments in pancreatic cancer.Matrix biology : journal of the International Society for Matrix Biology · 2025Article
- HypoxamiRs in pancreatic cancer: master regulators of the hypoxic tumor microenvironment.Cell biology and toxicology · 2025Review
- A RAS(ON) Multi-Selective Inhibitor Combination Therapy Triggers Long-term Tumor Control through Senescence-Associated Tumor-Immune Equilibrium in Pancreatic Ductal Adenocarcinoma.Cancer discovery · 2025Article
- Metastatic heterogeneity in pancreatic cancer: mechanisms and opportunities for targeted intervention.The Journal of clinical investigation · 2025Review
- Integrated Metabolomics and Spatial Transcriptomics of Cystic Pancreatic Cancer Precursors Reveals Dysregulated Polyamine Metabolism as a Biomarker of Progression.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
168 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundPancreatic ductal adenocarcinoma (PDA) is characterised by a robust desmoplasia, including the notable accumulation of immunosuppressive cells that shield neoplastic cells from immune detection. Immune evasion may be further enhanced if the malignant cells fail to express high levels of antigens that are sufficiently immunogenic to engender an effector T cell response.
objectiveTo investigate the predominant subsets of immunosuppressive cancer-conditioned myeloid cells that chronicle and shape the progression of pancreas cancer. We show that selective depletion of one subset of myeloid-derived suppressor cells (MDSC) in an autochthonous, genetically engineered mouse model (GEMM) of PDA unmasks the ability of the adaptive immune response to engage and target tumour epithelial cells.
methodsA combination of in vivo and in vitro studies were performed employing a GEMM that faithfully recapitulates the cardinal features of human PDA. The predominant cancer-conditioned myeloid cell subpopulation was specifically targeted in vivo and the biological outcomes determined.
resultsPDA orchestrates the induction of distinct subsets of cancer-associated myeloid cells through the production of factors known to influence myelopoiesis. These immature myeloid cells inhibit the proliferation and induce apoptosis of activated T cells. Targeted depletion of granulocytic MDSC (Gr-MDSC) in autochthonous PDA increases the intratumoral accumulation of activated CD8 T cells and apoptosis of tumour epithelial cells and also remodels the tumour stroma.
conclusionsNeoplastic ductal cells of the pancreas induce distinct myeloid cell subsets that promote tumour cell survival and accumulation. Targeted depletion of a single myeloid subset, the Gr-MDSC, can unmask an endogenous T cell response, disclosing an unexpected latent immunity and invoking targeting of Gr-MDSC as a potential strategy to exploit for treating this highly lethal disease.
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Registered trials
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.