ArticleCancer science2020
Lipid accumulation in macrophages confers protumorigenic polarization and immunity in gastric cancer.
Article in Cancer science, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.
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Who cites it
87 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Targeting PI3K-gamma in myeloid driven tumour immune suppression: a systematic review and meta-analysis of the preclinical literature.Cancer immunology, immunotherapy : CII · 2024Pooled it
- The Efferocytosis-Driven Macrophage Polarization: A Concerto in the Tumor Immunosuppressive Microenvironment.MedComm · 2026Review
- Targeting the SELP/PSGL1 axis reprograms M2 macrophages and enhances anti-PD-1 efficacy in gastric cancer.Oncogene · 2026Article
- Myeloid deficiency of RORα exacerbates lipid dysregulation and laser-induced choroidal neovascularization.Angiogenesis · 2026Article
- Lipidomic Profiling Reveals Stage-Associated Triglyceride Accumulation in Macrophages in a Mouse Model of Ovarian Cancer.Cancers · 2026Article
- New Functions of Mitochondrial Dysfunction in Gastric Cancer: From Molecular Processes to Potential Treatments.International journal of molecular sciences · 2026Review
- Targeting the cancer metabolism-immunity interface: update and perspectives.Experimental hematology & oncology · 2026Review
- Circ_0001313 promotes an immunosuppressive tumor microenvironment through GM-CSF-associated granulocytic myeloid cell activation in colorectal cancer.Discover oncology · 2026Article
- Gastric Cancer: Pathobiology and Therapeutics.MedComm · 2026Review
- Multiomics immune profiling of a patient-relevant orthotopic lung cancer model using SEPARATE-Seq.Nature communications · 2026Article
- M2-polarized tumor-associated macrophages as key orchestrators of gastric cancer pathogenesis and therapeutic resistance.Discover oncology · 2026Review
- The PI3K-AKT pathway mediates the imbalance of bone marrow macrophage polarization in patients with immune thrombocytopenia.Journal of translational medicine · 2026Article
- Lipid droplets are rigid and physically suppress phagocytosis, unless cell compression or stretching activates actomyosin.Molecular biology of the cell · 2026Article
- Tumor microenvironment dynamics in gastric cancer pathogenesis and therapeutic resistance.Molecular cancer · 2026Review
- Targeting Tumor-Associated Macrophages to Reshape the Immuno-Mechanical Landscape: Molecular Mechanisms and Therapeutic Strategies.International journal of biological sciences · 2026Review
- The metabolic environment within solid tumors drives a complex crosstalk between macrophages and NK cells.Frontiers in immunology · 2026Review
- Lipid metabolic plasticity in glioblastoma: mechanisms, tumor microenvironment remodeling, and therapeutic opportunities.Frontiers in oncology · 2026Review
- Host-related Determinants of Response to Immunotherapy in Non-small Cell Lung Cancer: The Interplay of Body Composition, Metabolism, Sex and Immune Regulation.Current oncology reports · 2025Review
- GPR34 inhibition reprograms tumor-associated macrophages and enhances the sensitivity of anti-PD-1 therapy in hepatocellular carcinoma.Cancer cell international · 2025Article
- Lactate and lactylation: molecular insights into histone and non-histone lactylation in tumor progression, tumor immune microenvironment, and therapeutic strategies.Biomarker research · 2025Review
27 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors.
Funding
Abstract
Heterotypic interactions between tumor cells and macrophages can enable tumor progression and hold potential for the development of therapeutic interventions. However, the communication between tumors and macrophages and its mechanism are poorly understood. Here, we find that tumor-associated macrophages (TAM) from tumor-bearing mice have high amounts of lipid as compared to macrophages from tumor-free mice. TAM also present high lipid content in clinical human gastric cancer patients. Functionally, TAM with high lipid levels are characterized by polarized M2-like profiling, and exhibit decreased phagocytic potency and upregulated programmed death ligand 1 (PD-L1) expression, blocking anti-tumor T cell responses to support their immunosuppressive function. Mechanistically, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis identifies the specific PI3K pathway enriched within lipid-laid TAM. Lipid accumulation in TAM is mainly caused by increased uptake of extracellular lipids from tumor cells, which leads to the upregulated expression of gamma isoform of phosphoinositide 3-kinase (PI3K-γ) polarizing TAM to M2-like profiling. Correspondingly, a preclinical gastric cancer model is used to show pharmacological targeting of PI3K-γ in high-lipid TAM with a selective inhibitor, IPI549. IPI549 restores the functional activity of macrophages and substantially enhances the phagocytosis activity and promotes cytotoxic-T-cell-mediated tumor regression. Collectively, this symbiotic tumor-macrophage interplay provides a potential therapeutic target for gastric cancer patients through targeting PI3K-γ in lipid-laden TAM.
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