ArticleJCI insight2022
Targeting TNF-α-producing macrophages activates antitumor immunity in pancreatic cancer via IL-33 signaling.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- High IntratumoralInternational journal of molecular sciences · 2026Pooled it
- Decoding spatiotemporal fibrotic and cellular immunosuppression of therapeutic T cells in live pancreatic ductal adenocarcinoma.Molecular systems biology · 2026Article
- TRANCE is a unique marker of chronic pancreatitis in children.JCI insight · 2026Article
- Targeting CCR1 Remodels the Tumor Microenvironment and Relieves Immunosuppression in Pancreatic Cancer.Cancer immunology research · 2026Article
- Neutrophil-Macrophage Interactions Shape Inflammatory Macrophage Remodeling in Gastric Cancer During Chemo-Immunotherapy.Cancer science · 2026Article
- Pancreatic cancer induces B cell lineage plasticity via Pax5 inhibition to sustain immunosuppression.Cell death discovery · 2026Article
- Article
- Role of tumor microenvironment in regulator of tumor progression and immunotherapy.Discover oncology · 2026Review
- Decoding Pancreatic Cancer Pain: From Tumor-Nerve Crosstalk to Targeted Analgesic Strategies.International journal of medical sciences · 2026Review
- CCR-CCL axes as key upstream influencers of pancreatic ductal adenocarcinoma: CCR2-CCL2, CCR5-CCL5, CCR4-CCL17/22, CCR6-CCL20, CCR7-CCL19/21.Frontiers in immunology · 2026Review
- Irreversible electroporation with intratumoral plant virus immunotherapy induces systemic immunity in a metastatic model of pancreatic cancer.Cancer letters · 2025Article
- Extracellular matrix architecture promotes immunosuppressive microenvironments in pancreatic cancer.Matrix biology : journal of the International Society for Matrix Biology · 2025Article
- Neutrophil Extracellular Traps Modulate Recruitment and Immunosuppression of Macrophages in Pancreatic Adenocarcinoma.Cancer immunology research · 2025Article
- Unlocking IL-33: New Insights into Tumor Immunity.Immune network · 2025Review
- Computationally Enabled Polychromatic Polarized Imaging Enables Mapping of Matrix Architectures that Promote Pancreatic Ductal Adenocarcinoma Dissemination.The American journal of pathology · 2025Article
- A phase 0, window of opportunity study of parasympathetic stimulation with bethanechol in localized pancreatic adenocarcinoma prior to surgery.The oncologist · 2025Article
- Improving outcomes of patients with pancreatic cancer.Nature reviews. Clinical oncology · 2025Review
- Decitabine co-operates with the IL-33/ST2 axis modifying the tumor microenvironment and improving the response to PD-1 blockade in melanoma.Journal of experimental & clinical cancer research : CR · 2025Article
- Inflammation, microbiota, and pancreatic cancer.Cancer cell international · 2025Review
- Spatial tumor immune heterogeneity facilitates subtype co-existence and therapy response in pancreatic cancer.Nature communications · 2025Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDA) remains resistant to immune therapies, largely owing to robustly fibrotic and immunosuppressive tumor microenvironments. It has been postulated that excessive accumulation of immunosuppressive myeloid cells influences immunotherapy resistance, and recent studies targeting macrophages in combination with checkpoint blockade have demonstrated promising preclinical results. Yet our understanding of tumor-associated macrophage (TAM) function, complexity, and diversity in PDA remains limited. Our analysis reveals significant macrophage heterogeneity, with bone marrow-derived monocytes serving as the primary source for immunosuppressive TAMs. These cells also serve as a primary source of TNF-α, which suppresses expression of the alarmin IL-33 in carcinoma cells. Deletion of Ccr2 in genetically engineered mice decreased monocyte recruitment, resulting in profoundly decreased TNF-α and increased IL-33 expression, decreased metastasis, and increased survival. Moreover, intervention studies targeting CCR2 with a new orthosteric inhibitor (CCX598) rendered PDA susceptible to checkpoint blockade, resulting in reduced metastatic burden and increased survival. Our data indicate that this shift in antitumor immunity is influenced by increased levels of IL-33, which increases dendritic cell and cytotoxic T cell activity. These data demonstrate that interventions to disrupt infiltration of immunosuppressive macrophages, or their signaling, have the potential to overcome barriers to effective immunotherapeutics for PDA.
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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.