ArticleCancer discovery2020
Regulatory T-cell Depletion Alters the Tumor Microenvironment and Accelerates Pancreatic Carcinogenesis.
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Article in Cancer discovery, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 253 papers, 1 of them a synthesis that pooled it.
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253citing papers in PubMed, 1 pooled it
19.9field-weighted citation impact, top 1% of its field
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Who cites it
253 citing papers in PubMed, 1 synthesis or guideline pooled it, 366 citations in OpenAlex.
- 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
- Cytokine fusion proteins for solid tumor therapy: mechanistic insights and clinical advances.Journal of hematology & oncology · 2026Review
- Regulatory T cell induction strategies and applications in the treatment of immune and non-immune diseases.Signal transduction and targeted therapy · 2026Review
- Article
- Targeting the αvβ5 Integrin Modifies the TGFβ-Rich Tumor Microenvironment of Pancreatic Cancer.Cancer research · 2026Article
- Targeting CCR1 Remodels the Tumor Microenvironment and Relieves Immunosuppression in Pancreatic Cancer.Cancer immunology research · 2026Article
- Pancreatic Cancer-Advances in the Last 50 Years.World journal of surgery · 2026Review
- Treg-derived exosomal miR-146a orchestrates bidirectional Treg-CAF crosstalk to sustain immunosuppressive tumor microenvironments.Medical oncology (Northwood, London, England) · 2026Review
- Molecular phenotypes and spatial archetypes: A new framework for cancer-associated fibroblasts.Cancer cell · 2026Review
- Antibody subclass deficiency accelerates tumorigenesis in genetically engineered mouse models of pancreatic cancer.JCI insight · 2026Article
- CAF-derived PAI-1 serves as an EGFR ligand and fuels KRAS-mutant pancreatic cancer.Nature communications · 2026Article
- APE1/Ref-1: multifunctional biology, selective inhibition, and the path to clinical translation.Expert opinion on therapeutic targets · 2026Review
- Tripartite motif containing 21 autoimmunity primes CD8Arthritis research & therapy · 2026Article
- Regulatory T cells in cancer and inflammation.Signal transduction and targeted therapy · 2026Review
- CA19-9 induces microenvironment remodeling in pancreatic ductal adenocarcinoma.bioRxiv : the preprint server for biology · 2026Article
- Quantitative 3D histology reveals localized immune remodeling during early pancreatic cancer progression.Cell press blue · 2026Article
- Homeobox A10 in gastrointestinal malignancies: unraveling metastatic mechanisms and novel therapeutic opportunities.Cancer metastasis reviews · 2026Review
- Pancreatic cancer.Nature reviews. Disease primers · 2026Review
- High-Throughput Phenotypic Screen to Identify FoxP3 Regulators in Primary T Cells.ACS chemical biology · 2026Article
193 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors at 1 institution in 1 country.
Yaqing ZhangDepartment of Surgery, University of Michigan, Ann Arbor, Michigan. marinapa@umich.edu filipb@umich.edu yaqingzh@umich.edu.ORCID https://orcid.org/0000-0002-9185-4364
Jenny LazarusDepartment of Surgery, University of Michigan, Ann Arbor, Michigan.
Nina G SteeleDepartment of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan.
Wei YanDepartment of Surgery, University of Michigan, Ann Arbor, Michigan.
Ho-Joon LeeDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan.ORCID https://orcid.org/0000-0003-3616-5387
Zeribe C NwosuDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan.
Christopher J HalbrookDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan.ORCID https://orcid.org/0000-0002-3376-3114
Rosa E MenjivarProgram in Cellular and Molecular Biology, University of Michigan, Ann Arbor, Michigan.
Samantha B KempMolecular and Cellular Pathology Graduate Program, University of Michigan, Ann Arbor, Michigan.
Veerin R SirihorachaiCancer Biology Program, University of Michigan, Ann Arbor, Michigan.
Ashley Velez-DelgadoDepartment of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan.
Katelyn DonahueCancer Biology Program, University of Michigan, Ann Arbor, Michigan.
Eileen S CarpenterDepartment of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan.
Kristee L BrownDepartment of Surgery, University of Michigan, Ann Arbor, Michigan.
Valerie Irizarry-NegronDepartment of Surgery, University of Michigan, Ann Arbor, Michigan.
Anna C NevisonDepartment of Surgery, University of Michigan, Ann Arbor, Michigan.
Alekya VintaCollege of Literature, Science, and the Arts, University of Michigan, Ann Arbor, Michigan.
Michelle A AndersonDepartment of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan.
Howard C CrawfordRogel Cancer Center, University of Michigan, Ann Arbor, Michigan.
Costas A LyssiotisRogel Cancer Center, University of Michigan, Ann Arbor, Michigan.ORCID https://orcid.org/0000-0001-9309-6141
Timothy L FrankelDepartment of Surgery, University of Michigan, Ann Arbor, Michigan.
Filip BednarDepartment of Surgery, University of Michigan, Ann Arbor, Michigan. marinapa@umich.edu filipb@umich.edu yaqingzh@umich.edu.ORCID https://orcid.org/0000-0001-5193-9817
Marina Pasca di MaglianoDepartment of Surgery, University of Michigan, Ann Arbor, Michigan. marinapa@umich.edu filipb@umich.edu yaqingzh@umich.edu.ORCID https://orcid.org/0000-0001-9632-9035
University of Michigan · US
Funding
XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI THEODORE S LAWRENCE · 1988 to 2026
$178.2MUniversity of Michigan Center for Gastrointestinal ResearchP30DK034933 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI OWYANG, CHUNG · 1986 to 2021
$22.5MCELLULAR AND MOLECULAR BIOLOGY AT MICHIGANT32GM007315 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PUTHENVEEDU, MANOJKUMAR A · 1985 to 2021
$12.8MTraining Program in Tumor MicroenvironmentT32CA009676 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Maria G Castro, Analisa Virginia DiFeo · 1992 to 2026
$7.3MUniversity of Michigan Postbaccalaureate Research Education Program (UM PREP)R25GM086262 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ALLEN, BENJAMIN · 2009 to 2024
$6.1MTraining in Basic and Translational Digestive SciencesT32DK094775 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI JOHN Y KAO, LINDA C. SAMUELSON · 2012 to 2026
$3.6MMechanisms of Pancreatic Inflammation, Tissue Repair and CarcinogenesisR01CA151588 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PASCA DI MAGLIANO, MARINA · 2010 to 2020
$3.3MCellular Biotechnology Training Program (CBTP) - Years 31-35T32GM145304 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Guizhi Zhu · 2022 to 2026
$2.6MInterrupting Cellular Crosstalk in the Immunosuppressive Microenvironment of Pancreas CancerU01CA224145 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CRAWFORD, HOWARD C., PASCA DI MAGLIANO, MARINA · 2017 to 2021
$2.6MIntratumoral Metabolic Crosstalk Promotes Therapeutic Resistance in Pancreatic CancerR37CA237421 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Costas Andreas Lyssiotis · 2020 to 2026
$2.6MDosage-Dependent Hedgehog Signaling in Pancreatic CancerR01CA198074 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ALLEN, BENJAMIN, PASCA DI MAGLIANO, MARINA · 2015 to 2019
$1.9MTraining Program in Translational ResearchT32GM113900 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LIEBERMAN, ANDREW P, NIKOLOVSKA-COLESKA, ZANETA · 2016 to 2020
$991kNCI NIH HHS F32 CA228328NCI NIH HHS K08 CA201581NCI NIH HHS L30 CA188846NCI NIH HHS P30 CA046592NCI NIH HHS R01 CA151588NCI NIH HHS R01 CA198074NCI NIH HHS R37 CA237421NCI NIH HHS R50 CA232985NCI NIH HHS T32 CA009676NCI NIH HHS U01 CA224145NIDDK NIH HHS P30 DK034933NIDDK NIH HHS T32 DK094775NIGMS NIH HHS R25 GM086262NIGMS NIH HHS T32 GM007315NIGMS NIH HHS T32 GM113900NIGMS NIH HHS T32 GM145304
Abstract
Regulatory T cells (Treg) are abundant in human and mouse pancreatic cancer. To understand the contribution to the immunosuppressive microenvironment, we depleted Tregs in a mouse model of pancreatic cancer. Contrary to our expectations, Treg depletion failed to relieve immunosuppression and led to accelerated tumor progression. We show that Tregs are a key source of TGFβ ligands and, accordingly, their depletion reprogramed the fibroblast population, with loss of tumor-restraining, smooth muscle actin-expressing fibroblasts. Conversely, we observed an increase in chemokines
Indexed as
AnimalsCarcinogenesisChemokine CCL3Chemokine CCL8Chemokines, CCDisease Models, AnimalFibroblastsHumansMicePancreasPancreatic NeoplasmsReceptors, CCR1T-Lymphocytes, RegulatoryTransforming Growth Factor betaTumor MicroenvironmentCcl3 protein, mouseCcl6 protein, mouseCcl8 protein, mouseCcr1 protein, mouseChemokine CCL3Chemokine CCL8Chemokines, CCReceptors, CCR1Transforming Growth Factor beta
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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.