ArticleNature immunology2021
Tumor-induced reshuffling of lipid composition on the endoplasmic reticulum membrane sustains macrophage survival and pro-tumorigenic activity.
Article in Nature immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers, 2 of them syntheses that pooled it.
What it found
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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.
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Who cites it
128 citing papers in PubMed, 2 syntheses or guidelines pooled it, 197 citations in OpenAlex.
- Controlling nutritional status score predicts clinical outcome in cancer patients treated with immune checkpoint inhibitor: a systematic review and meta-analysis.Frontiers in immunology · 2026Pooled it
- The role of lipid metabolic reprogramming in tumor microenvironment.Theranostics · 2023Pooled it
- Integrated multi-omics analysis reveals the molecular landscape and therapeutic strategies in Chinese cervical cancer patients.PLoS biology · 2026Article
- Senescence-directed nanotherapy ameliorates fibrosis and overcomes immune exclusion in cancer.Science (New York, N.Y.) · 2026Article
- Nuclear Medicine Tracers Targeting Tumor-Associated Macrophages.Pharmaceutics · 2026Review
- Targeting PID1 generates oxysterols to switch macrophage cell fates for improved antitumor immunity.Nature cancer · 2026Article
- The unfolded protein sensor IRE1 is essential for homeostatic dendritic cell maturation.Nature communications · 2026Article
- Rethinking LPCAT3 roles in human disease: broadening perspectives beyond ferroptosis.Cell death & disease · 2026Review
- Article
- Advances in immune cell-based therapeutic agents for the treatment of inflammation-related diseases.Acta pharmaceutica Sinica. B · 2026Review
- Lipid metabolism reprogramming shapes the immune landscape in the tumor microenvironment.Cellular & molecular immunology · 2026Review
- Endoplasmic reticulum stress in antitumor immunity and immunotherapy resistance: mechanisms and therapeutic implications.Molecular cancer · 2026Review
- Harnessing lipid-driven immunometabolic pathways in omental metastases to enhance immunotherapy in patients with ovarian cancer.Signal transduction and targeted therapy · 2026Article
- Decoding the Role of Lipid Metabolism and Membrane Dynamics in Melanoma.International journal of molecular sciences · 2026Review
- Targeting the UPR with Small Molecules: Emerging Strategies for Immune Regulation.Molecules (Basel, Switzerland) · 2026Review
- An updated overview of lipid-regulated immunobiology in macrophages.Acta biochimica et biophysica Sinica · 2026Review
- Tumor-immune metabolic tug-of-war: from immune escape to targeting metabolic rewiring in cancer therapy.Frontiers in cell and developmental biology · 2026Review
- Lipid metabolic plasticity in glioblastoma: mechanisms, tumor microenvironment remodeling, and therapeutic opportunities.Frontiers in oncology · 2026Review
- Immunometabolic programming of macrophages and tumor-associated macrophages: metabolic pathways shaping polarization, immune regulation, and disease outcomes.Frontiers in immunology · 2026Review
- Lovastatin Targets LIPA to Induce ER Stress-Mediated Apoptosis in Acute Myeloid Leukemia: A Multi-Omics Study.International journal of general medicine · 2026Article
68 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 6 institutions in 6 countries.
Funding
Abstract
Tumor-associated macrophages (TAMs) display pro-tumorigenic phenotypes for supporting tumor progression in response to microenvironmental cues imposed by tumor and stromal cells. However, the underlying mechanisms by which tumor cells instruct TAM behavior remain elusive. Here, we uncover that tumor-cell-derived glucosylceramide stimulated unconventional endoplasmic reticulum (ER) stress responses by inducing reshuffling of lipid composition and saturation on the ER membrane in macrophages, which induced IRE1-mediated spliced XBP1 production and STAT3 activation. The cooperation of spliced XBP1 and STAT3 reinforced the pro-tumorigenic phenotype and expression of immunosuppressive genes. Ablation of XBP1 expression with genetic manipulation or ameliorating ER stress responses by facilitating LPCAT3-mediated incorporation of unsaturated lipids to the phosphatidylcholine hampered pro-tumorigenic phenotype and survival in TAMs. Together, we uncover the unexpected roles of tumor-cell-produced lipids that simultaneously orchestrate macrophage polarization and survival in tumors via induction of ER stress responses and reveal therapeutic targets for sustaining host antitumor immunity.
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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.