The impact of the expression level of growth differentiation factor 15 in tumor tissue on the response to immunotherapy in non-small cell lung cancer.

Autor: Akdogan O; Faculty of Medicine, Department of Medical Oncology, Gazi University, Ankara, Turkey. orhunakdogan@gmail.com., Ogut B; Faculty of Medicine, Department of Pathology, Gazi University, Ankara, Turkey., Sutcuoglu O; Faculty of Medicine, Department of Medical Oncology, Gazi University, Ankara, Turkey., Sert A; Faculty of Medicine, Department of Pathology, Gazi University, Ankara, Turkey., Gurler F; Faculty of Medicine, Department of Medical Oncology, Gazi University, Ankara, Turkey., Akyurek N; Faculty of Medicine, Department of Pathology, Gazi University, Ankara, Turkey., Ozdemir N; Faculty of Medicine, Department of Medical Oncology, Gazi University, Ankara, Turkey., Ozet A; Faculty of Medicine, Department of Medical Oncology, Gazi University, Ankara, Turkey., Yazici O; Faculty of Medicine, Department of Medical Oncology, Gazi University, Ankara, Turkey.
Jazyk: angličtina
Zdroj: BMC cancer [BMC Cancer] 2024 Aug 05; Vol. 24 (1), pp. 954. Date of Electronic Publication: 2024 Aug 05.
DOI: 10.1186/s12885-024-12727-3
Abstrakt: Background: Growth differentiation factor-15 (GDF-15), a member of the TGF-β superfamily, is overexpressed in various cancers and facilitates immune evasion by inhibiting T-cell activation. GDFATHER-TRIAL's phase 2a results demonstrated promising outcomes when combining the GDF-15 neutralizing antibody visugromab (CTL002) with nivolumab, enhancing the response to immunotherapy. This study evaluated the prognostic significance of GDF-15 expression in non-small cell lung cancer (NSCLC) tumor tissues in terms of immunotherapy response.
Methods: This retrospective study included 50 patients with metastatic NSCLC treated with nivolumab at Gazi University Hospital between January 2021 and July 2023. GDF-15 expression was evaluated using immunochemistry staining and categorized based on the intensity of cytoplasmic or membranous staining. Samples were divided into a low expression group (scores 0 and 1) and a high expression group (scores 2 and 3). The primary outcomes were progression-free survival (PFS) and overall survival (OS), which were analyzed using Kaplan‒Meier and Cox proportional hazards models. Objective response rates were assessed in secondary outcomes.
Results: Of the 50 patients, 43 were men (86%), with a median age of 63.9 years. Half of the patients exhibited low GDF-15 expression. High GDF-15 expression correlated with shorter PFS and OS. The median PFS was 7.8 months for the low-expression group versus 4.4 months for the high-expression group (HR, 0.41; 95% CI, 0.20-0.83; p = 0.013). The median OS was 18.1 months for the low-expression group compared to 11.8 months for the high-expression group (HR, 0.36; 95% CI, 0.16-0.78; p = 0.007). The objective response rate was significantly greater in the low GDF-15 group (52%) than in the high GDF-15 group (24%) (p = 0.040).
Conclusion: Elevated GDF-15 expression in NSCLC tumor tissues is associated with poorer response to nivolumab, suggesting that GDF-15 is a potential prognostic biomarker for immunotherapy efficacy. These findings warrant further validation through prospective studies to optimize treatment strategies for NSCLC patients.
(© 2024. The Author(s).)
Databáze: MEDLINE
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