ArticleThoracic cancer2025
Desensitizing Effect of Intra-Tumoral GDF-15 on Immunotherapy in Patients With Advanced Non-Small Cell Lung Cancer.
Article in Thoracic cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- GDF15: A Hijacked Metabo-Hormone Orchestrating Cachexia and Immunosuppression in Cancer.Biomolecules · 2026Review
- Convergent Roles of Growth Differentiation Factor-15 (GDF-15) in Mechanotransduction, Vascular Disorganization, and Immune Suppression in Melanoma.bioRxiv : the preprint server for biology · 2026Article
- GDF15 as a sentinel of metabolic integrity: a narrative review of stress signaling, multisystem pathophysiology, and therapeutic potential.Frontiers in endocrinology · 2026Review
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Authors and funding
15 authors.
Funding
Abstract
backgroundSerum growth/differentiation factor 15 (GDF-15) suppresses anti-tumor immunity and predicts prognosis in several malignancies. Elevated GDF-15 levels are linked to cancer cachexia, characterized by weight loss and systemic inflammation, adversely affecting patient outcomes and therapy response. However, serum GDF-15 is not always derived from tumor tissues but also from multiple organs. Therefore, we evaluated whether intra-tumoral GDF-15 could be used as a biomarker for immunotherapy and its potential association with cancer cachexia.
methodWe retrospectively evaluated patients with advanced non-small cell lung cancer (NSCLC) who underwent treatment with programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) inhibitors at the Shizuoka Cancer Center between 2017 and 2021. Patients with histologically confirmed NSCLC (stage III-IV or postoperative recurrence) who had undergone biopsy or surgery within 6 months prior to initiating immunotherapy were included. Expression of tumor-derived GDF-15 was evaluated using immunohistochemical staining of archival biopsy and surgical specimens. We analyzed the correlation between intra-tumoral GDF-15 expression and the incidence of cancer cachexia, as well as its impact on progression-free survival (PFS) and overall survival (OS).
resultIn 6 of 35 cases, tumor cells highly expressed GDF-15. Patients with high intra-tumoral GDF-15 expression had a higher incidence of cancer cachexia (100% vs. 41.4%, p < 0.05), shorter PFS (3.4 vs. 13.4 months, p < 0.05), and shorter OS (9.5 vs. 26.5 months, p < 0.05) than those with low intra-tumoral GDF-15 expression.
conclusionIntra-tumoral GDF-15 expression may predict the presence of cancer cachexia and the efficacy of PD-1/PD-L1 inhibitors in patients with advanced non-small cell lung cancer.
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