ArticleJournal for immunotherapy of cancer2021
GDF15 induces immunosuppression via CD48 on regulatory T cells in hepatocellular carcinoma.
Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers, 1 of them a synthesis that pooled it.
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Who cites it
110 citing papers in PubMed, 1 synthesis or guideline pooled it, 165 citations in OpenAlex.
- GDF-15 as a biomarker for diagnosis and prognosis of lung cancer: a meta-analysis.Frontiers in oncology · 2025Pooled it
- First-in-Human Study to Evaluate the Safety and Efficacy of Anti-GDF15 Antibody AZD8853 in Patients with Advanced/Metastatic Solid Tumors.Cancer research communications · 2025Trial
- Trial
- Targeting the Tumor Microenvironment Network to Overcome Immunotherapy Resistance in Non-Small Cell Lung Cancer: Mechanisms to Clinical Translation.Cancer medicine · 2026Review
- Article
- Plasma GDF-15 Levels Are Associated With HIV Reservoir Markers Independently of Inflammation in People With HIV on Antiretroviral Therapy.The Journal of infectious diseases · 2026Article
- Nanobody-based characterization of Galectin-13 reveals immunomodulatory and tumor-promoting functions.The Journal of biological chemistry · 2026Article
- GDF15 Reprograms the Microenvironment to Drive Liver Metastasis of Uveal Melanoma.Cancer research · 2026Article
- Nicotinamide riboside enhances adoptive T cell therapy by promoting memory differentiation and metabolic fitness.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- GDF15: A Hijacked Metabo-Hormone Orchestrating Cachexia and Immunosuppression in Cancer.Biomolecules · 2026Review
- GDF15 in Liver Fibrosis: Molecular Mechanisms, Immunoregulatory Functions, and Therapeutic Potential.Biomolecules · 2026Review
- Osteocyte-Derived GDF15 Promotes Paclitaxel Resistance, Tumor Growth, and Bone Microenvironment Regulation in Prostate Cancer.Current issues in molecular biology · 2026Article
- Regulatory T cells in cancer and inflammation.Signal transduction and targeted therapy · 2026Review
- Gdf15 expression in thermogenic adipocytes regulates diet-induced weight gain in a sex-dependent manner.Molecular medicine (Cambridge, Mass.) · 2026Article
- Research progress on the biological function and molecular mechanism of GDF-15 in solid malignant tumors.World journal of surgical oncology · 2026Review
- Context-Dependent Role of GDF15: GDF15Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- GFRAL is required to mediate changes in systemic metabolism in response to mitochondrial stress in brown adipose tissue.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Treg-γδ T cell axis determines sexual dimorphism in hepatocarcinogenesis.Nature communications · 2026Article
- GDF-15 Levels in Cirrhosis Are Linked to Hepatic Fibrogenesis, Bacterial Translocation, and Worse Clinical Outcomes.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- Antibody screening for tumor and immune hotspot targets: The frontier of new methods and technologies.Journal of pharmaceutical analysis · 2026Review
50 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundA better understanding of the molecular mechanisms that manifest in the immunosuppressive tumor microenvironment (TME) is crucial for developing more efficacious immunotherapies for hepatocellular carcinoma (HCC), which has a poor response to current immunotherapies. Regulatory T (Treg) cells are key mediators of HCC-associated immunosuppression. We investigated the selective mechanism exploited by HCC that lead to Treg cells expansion and to find more efficacious immunotherapies.
methodsWe used matched tumor tissues and blood samples from 150 patients with HCC to identify key factors of Treg cells expansion. We used mass cytometry (CyTOF) and orthotopic cancer mouse models to analyze overall immunological changes after growth differentiation factor 15 (GDF15) gene ablation in HCC. We used flow cytometry, coimmunoprecipitation, RNA sequencing, mass spectrum, chromatin immunoprecipitation and
resultsGDF15 is positively associated with the elevation of Treg cell frequencies in patients wih HCC. Gene ablation of GDF15 in HCC can convert an immunosuppressive TME to an inflammatory state. GDF15 promotes the generation of peripherally derived inducible Treg (iTreg) cells and enhances the suppressive function of natural Treg (nTreg) cells by interacting with a previously unrecognized receptor CD48 on T cells and thus downregulates STUB1, an E3 ligase that mediates forkhead box P3 (FOXP3) protein degradation. GDF15 neutralizing antibody effectively eradicates HCC and augments the antitumor immunity in mouse.
conclusionsOur results reveal the generation and function enhancement of Treg cells induced by GDF15 is a new mechanism for HCC-related immunosuppression. CD48 is the first discovered receptor of GDF15 in the immune system which provide the possibility to solve the molecular mechanism of the immunomodulatory function of GDF15. The therapeutic GDF15 blockade achieves HCC clearance without obvious adverse events.
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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.