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Growth/Differentiation Factor-15 (GDF-15): From Biomarker to Novel Targetable Immune Checkpoint
Open accessAbstract
Growth/differentiation factor-15 (GDF-15), also named macrophage inhibitory cytokine-1, is a divergent member of the transforming growth factor β superfamily. While physiological expression is barely detectable in most somatic tissues in humans, GDF-15 is abundant in placenta. Elsewhere, GDF-15 is often induced under stress conditions, seemingly to maintain cell and tissue homeostasis; however, a moderate increase in GDF-15 blood levels is observed with age. Highly elevated GDF-15 levels are mostly linked to pathological conditions including inflammation, myocardial ischemia, and notably cancer. GDF-15 has thus been widely explored as a biomarker for disease prognosis. Mechanistically, induction of anorexia via the brainstem-restricted GDF-15 receptor GFRAL (glial cell-derived neurotrophic factor [GDNF] family receptor α-like) is well-documented. GDF-15 and GFRAL have thus become attractive targets for metabolic intervention. Still, several GDF-15 mediated effects (including its physiological role in pregnancy) are difficult to explain via the described pathway. Hence, there is a clear need to better understand non-metabolic effects of GDF-15. With particular emphasis on its immunomodulatory potential this review discusses the roles of GDF-15 in pregnancy and in pathological conditions including myocardial infarction, autoimmune disease, and specifically cancer. Importantly, the strong predictive value of GDF-15 as biomarker may plausibly be linked to its immune-regulatory function. The described associations and mechanistic data support the hypothesis that GDF-15 acts as immune checkpoint and is thus an emerging target for cancer immunotherapy.
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“Elevated levels of GDF15 have been linked to tumor growth and poor prognosis in cancer patients raising the question as to whether GDF15 serves as a tumor suppressor or promoter and a target for the treatment of cancer (84, 85, 99).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [85]
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Metadata
- Authors
- Wischhusen, J., Melero, I., & Fridman, W. H.
- Affiliations
- University of Würzburg (DE)
- Clinica Universidad de Navarra (ES)
- Inserm (FR)
- Corresponding author
- Wischhusen, Jörg
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2020-05-19
- Volume
- 11
- Pages
- 951-951
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC7248355
- OpenAlex
- W3026163675
- Cited by
- 506
- References
- 203
- Citations by year
- 2026: 79 · 2025: 94 · 2024: 112 · 2023: 79 · 2022: 84 · 2021: 49 · 2020: 9
- FWCI
- 8.60
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Deposito Adademico Digital Universidad De Navarra (University of Navarra) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Online Publication Service of Würzburg University (Würzburg University) (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › GDF15 and Related Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- GDF15, MIC-1, GFRAL, immune checkpoint, cancer immunotherapy, biomarkers, immunomodulation, pregnancy, myocardial infarction, autoimmune disease, inflammation, anorexia, TGF-beta superfamily
- MeSH terms
- Immune Checkpoint Inhibitors, Animals, Autoimmune Diseases, Female, Homeostasis, Humans, Myocardial Infarction, Neoplasms, Placenta, Pregnancy, Biomarkers, Mice, Growth Differentiation Factor 15, Immunomodulation
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