ArticleThe Journal of clinical investigation2017
NF-κB regulates GDF-15 to suppress macrophage surveillance during early tumor development.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 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.
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
106 citing papers in PubMed, 2 syntheses or guidelines pooled it, 172 citations in OpenAlex.
- GDF-15 as a biomarker for diagnosis and prognosis of lung cancer: a meta-analysis.Frontiers in oncology · 2025Pooled it
- Dietary inflammatory index and pancreatic cancer risk: a systematic review and dose-response meta-analysis.Public health nutrition · 2021Pooled it
- Trial
- Allostatic load, genetic susceptibility, and lung cancer risk: Evidence from a prospective cohort and integrative proteomic analyses.PLOS digital health · 2026Article
- High-Intensity Statin Treatment Is Associated With Reduced Growth Differentiation Factor-15 in Patients With Coronary Artery Disease.European journal of clinical investigation · 2026Observational
- GDF-15: Can It Be Used as a Biomarker in Acute Cerebrovascular Incidents?Journal of personalized medicine · 2026Article
- Context-Dependent Role of GDF15: GDF15Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Microproteins in Human Physiology and Pathology.Biochemistry · 2026Review
- A GDF-15-GFRAL axis controls autoimmune T cell responses during neuroinflammation.Nature immunology · 2026Article
- Paclitaxel drives TREM2Nature communications · 2026Article
- GDF15 as a sentinel of metabolic integrity: a narrative review of stress signaling, multisystem pathophysiology, and therapeutic potential.Frontiers in endocrinology · 2026Review
- Immunomodulatory functions of growth differentiation factor 15 in skin aging and inflammatory dermatoses.Frontiers in immunology · 2026Review
- Ageing, immune fitness and cancer.Nature reviews. Cancer · 2025Review
- New Horizons with Growth Differentiation Factor 15 in Oncology: From Cancer Cachexia and Tumour Immunity to Novel Therapeutic Strategies.Current oncology (Toronto, Ont.) · 2025Review
- Development of a serum protein biomarker panel for the diagnosis of pancreatic ductal adenocarcinoma using a machine learning approach.Scientific reports · 2025Article
- The blood lipidome fatty acid profile predicts the disease risk and clinical phenotypes of Alzheimer's disease: associations from two prospective cohort studies.Translational psychiatry · 2025Article
- Functional characteristics of fresh antitumor immune interferer GDF-15 in multiple cancers.Scientific reports · 2025Article
- MyoD is essential in rhabdomyosarcoma by promoting survival through differentiation and CYLD.iScience · 2025Article
- The Multifaceted Role of Growth Differentiation Factor 15 (GDF15): A Narrative Review from Cancer Cachexia to Target Therapy.Biomedicines · 2025Review
- GDF-15 Levels in Gouty Arthritis and Correlations with Decreasing Renal Function: A Clinical Study.Biomedicines · 2025Article
46 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
14 authors at 1 institution in 1 country.
Funding
Abstract
Macrophages are attracted to developing tumors and can participate in immune surveillance to eliminate neoplastic cells. In response, neoplastic cells utilize NF-κB to suppress this killing activity, but the mechanisms underlying their self-protection remain unclear. Here, we report that this dynamic interaction between tumor cells and macrophages is integrally linked by a soluble factor identified as growth and differentiation factor 15 (GDF-15). In vitro, tumor-derived GDF-15 signals in macrophages to suppress their proapoptotic activity by inhibiting TNF and nitric oxide (NO) production. In vivo, depletion of GDF-15 in Ras-driven tumor xenografts and in an orthotopic model of pancreatic cancer delayed tumor development. This delay correlated with increased infiltrating antitumor macrophages. Further, production of GDF-15 is directly regulated by NF-κB, and the colocalization of activated NF-κB and GDF-15 in epithelial ducts of human pancreatic adenocarcinoma supports the importance of this observation. Mechanistically, we found that GDF-15 suppresses macrophage activity by inhibiting TGF-β-activated kinase (TAK1) signaling to NF-κB, thereby blocking synthesis of TNF and NO. Based on these results, we propose that the NF-κB/GDF-15 regulatory axis is important for tumor cells in evading macrophage immune surveillance during the early stages of tumorigenesis.
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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.