ArticleThe Journal of experimental medicine2020
Type 1 conventional dendritic cells are systemically dysregulated early in pancreatic carcinogenesis.
Article in The Journal of experimental medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
123 citing papers in PubMed, 2 syntheses or guidelines pooled it, 171 citations in OpenAlex.
- Metabolic regulation and immunosuppressive functions of lipid-associated macrophages in pancreatic ductal adenocarcinoma.Frontiers in immunology · 2026Pooled it
- Mechanisms of obesity- and diabetes mellitus-related pancreatic carcinogenesis: a comprehensive and systematic review.Signal transduction and targeted therapy · 2023Pooled it
- Addition of Losartan to FOLFIRINOX and Chemoradiation Reduces Immunosuppression-Associated Genes, Tregs, and FOXP3+ Cancer Cells in Locally Advanced Pancreatic Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Trial
- Systemic inflammation is a determinant of outcomes of CD40 agonist-based therapy in pancreatic cancer patients.JCI insight · 2021Trial
- High-dimensional spectral flow cytometry uncovers progressive T-cell exhaustion and myeloid cell reprogramming in a CLL mouse model.HemaSphere · 2026Article
- Dendritic cell redundancy enables priming of anti-tumor CD4Cancer cell · 2026Article
- FAP-CD40 and PD1-IL2v combination therapy reprograms immunologically cold tumors through de novo intratumoral T cell-dendritic cell clusters.Journal for immunotherapy of cancer · 2026Article
- Article
- High-Dimensional Protein Analysis Uncovers Distinct Immunologic and Stromal Features in Primary and Metastatic Pancreatic Ductal Adenocarcinoma.Cancer research · 2026Article
- Article
- Exosomes and pancreatic diseases: mechanisms, applications, and challenges.European journal of medical research · 2026Review
- Agonistic CD40 elicits CD8+ T-cell-dependent primary responses and CD4+ T-cell-dependent long-term immunity in breast cancer.NPJ breast cancer · 2026Article
- Interleukin-6: The Unexpected Opponent to Pancreatic Cancer.Cellular and molecular gastroenterology and hepatology · 2026Article
- A Combinatorial Effect of Immune Checkpoint Inhibitors and CD40 Agonistic Antibody in Murine Pancreatic Cancer Model.Cancer science · 2026Article
- Tumor-Derived CDC37 Inhibits Antigen Cross-Presentation in Dendritic Cells and Impairs Anti-Tumor Immunity in Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Tubular epithelial cell-derived Flt3L is required for type 1 conventional dendritic cell (cDC1) activation and expansion in promoting the recovery in acute kidney injury.Journal of advanced research · 2025Article
- Combined Flt3L and CD40 agonism restores dendritic cell-driven T cell immunity in pancreatic cancer.Science immunology · 2025Article
- T-cell Dependency of Tumor Regressions and Complete Responses with RAS(ON) Multi-selective Inhibition in Preclinical Models of Pancreatic Ductal Adenocarcinoma.Cancer discovery · 2025Article
- Rewriting the dendritic cell code in cancer-from subset identity to immunotherapeutic design.FEBS letters · 2025Review
- Facts and Hopes of CD40 Agonists in Cancer Immunotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Review
63 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Type 1 conventional dendritic cells (cDC1s) are typically thought to be dysregulated secondarily to invasive cancer. Here, we report that cDC1 dysfunction instead develops in the earliest stages of preinvasive pancreatic intraepithelial neoplasia (PanIN) in the KrasLSL-G12D/+ Trp53LSL-R172H/+ Pdx1-Cre-driven (KPC) mouse model of pancreatic cancer. cDC1 dysfunction is systemic and progressive, driven by increased apoptosis, and results in suboptimal up-regulation of T cell-polarizing cytokines during cDC1 maturation. The underlying mechanism is linked to elevated IL-6 concomitant with neoplasia. Neutralization of IL-6 in vivo ameliorates cDC1 apoptosis, rescuing cDC1 abundance in tumor-bearing mice. CD8+ T cell response to vaccination is impaired as a result of cDC1 dysregulation. Yet, combination therapy with CD40 agonist and Flt3 ligand restores cDC1 abundance to normal levels, decreases cDC1 apoptosis, and repairs cDC1 maturation to drive superior control of tumor outgrowth. Our study therefore reveals the unexpectedly early and systemic onset of cDC1 dysregulation during pancreatic carcinogenesis and suggests therapeutically tractable strategies toward cDC1 repair.
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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.