ArticleeLife2022
Multiomic characterization of pancreatic cancer-associated macrophage polarization reveals deregulated metabolic programs driven by the GM-CSF-PI3K pathway.
Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 49 citations in OpenAlex.
- New insights into the ACLY-mediated metabolic and epigenetic interplay in macrophages.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Lactate-induced epithelial-mesenchymal transition: a metabolic nexus in pancreatic cancer metastasis.Translational cancer research · 2026Review
- Targeting CCR1 Remodels the Tumor Microenvironment and Relieves Immunosuppression in Pancreatic Cancer.Cancer immunology research · 2026Article
- KRASScience advances · 2026Article
- Decoding the CAF-TAM axis: multi-omics dissection and therapeutic targeting of stromal-immune crosstalk in the tumor microenvironment.Cell death & disease · 2026Review
- GOT1 Inhibition Induces Extracellular Matrix Remodeling in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- 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
- Tumor-immune metabolic tug-of-war: from immune escape to targeting metabolic rewiring in cancer therapy.Frontiers in cell and developmental biology · 2026Review
- GM-CSF promotes pro-inflammatory macrophage activation associated with Akt/mTOR signaling during experimental colitis.Frontiers in immunology · 2026Article
- Innate immunity-stroma crosstalk in pancreatic cancer: overcoming spatial and metabolic barriers to immunotherapy.Frontiers in immunology · 2026Review
- Targeting GM-CSF in Rheumatoid Arthritis: Advances in Cytokine-Directed Immunotherapy and Clinical Implications.Life (Basel, Switzerland) · 2025Review
- Oncotransformation in Bhas 42 Cell Transformation Assay by Typical Non-Genotoxic Carcinogens, PFOA and PFOS, and Time-Course Transcriptome Analysis.Biomolecules · 2025Article
- Precision immune regulation in KRAS-mutated cancers: the final piece of the puzzle?Journal of experimental & clinical cancer research : CR · 2025Review
- Tumor-educated cells in tumor microenvironment: Key drivers of immunotherapy resistance.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2025Article
- Tumor-associated macrophages (TAMs): Constructing an immunosuppressive microenvironment bridge for pancreatic ductal adenocarcinoma (PDAC).Cancer pathogenesis and therapy · 2025Review
- Delineation of signaling routes that underlie differences in macrophage phenotypic states.NAR molecular medicine · 2025Article
- Linking macrophage metabolism to function in the tumor microenvironment.Nature cancer · 2025Review
- TNFR1 signaling promotes pancreatic tumor growth by limiting dendritic cell number and function.Cell reports. Medicine · 2024Article
- Emergency myelopoiesis in solid cancers.British journal of haematology · 2024Review
- Systematic analysis of TREM2 and its carcinogenesis in pancreatic cancer.Translational cancer research · 2024Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
The pancreatic ductal adenocarcinoma microenvironment is composed of a variety of cell types and marked by extensive fibrosis and inflammation. Tumor-associated macrophages (TAMs) are abundant, and they are important mediators of disease progression and invasion. TAMs are polarized in situ to a tumor promoting and immunosuppressive phenotype via cytokine signaling and metabolic crosstalk from malignant epithelial cells and other components of the tumor microenvironment. However, the specific distinguishing features and functions of TAMs remain poorly defined. Here, we generated tumor-educated macrophages (TEMs) in vitro and performed detailed, multiomic characterization (i.e., transcriptomics, proteomics, metabolomics). Our results reveal unique genetic and metabolic signatures of TEMs, the veracity of which were queried against our in-house single-cell RNA sequencing dataset of human pancreatic tumors. This analysis identified expression of novel, metabolic TEM markers in human pancreatic TAMs, including ARG1, ACLY, and TXNIP. We then utilized our TEM model system to study the role of mutant Kras signaling in cancer cells on TEM polarization. This revealed an important role for granulocyte-macrophage colony-stimulating factor (GM-CSF) and lactate on TEM polarization, molecules released from cancer cells in a mutant Kras-dependent manner. Lastly, we demonstrate that GM-CSF dysregulates TEM gene expression and metabolism through PI3K-AKT pathway signaling. Collectively, our results define new markers and programs to classify pancreatic TAMs, how these are engaged by cancer cells, and the precise signaling pathways mediating polarization.
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