1. TGF-β mRNA levels in circulating extracellular vesicles are associated with response to anti-PD1 treatment in metastatic melanoma
- Author
-
Stefania Crucitta, Federico Cucchiara, Riccardo Marconcini, Alessandra Bulleri, Simona Manacorda, Annalisa Capuano, Dania Cioni, Amedeo Nuzzo, Evert de Jonge, Ron H. J. Mathjissen, Emanuele Neri, Ron H. N. van Schaik, Stefano Fogli, Romano Danesi, and Marzia Del Re
- Subjects
TGFβ ,immunotherapy ,melanoma ,extracellular vesicles ,liquid biopsy ,Biology (General) ,QH301-705.5 - Abstract
Introduction: Immune checkpoint inhibitors (ICIs) represent the standard therapy for metastatic melanoma. However, a few patients do not respond to ICIs and reliable predictive biomarkers are needed.Methods: This pilot study investigates the association between mRNA levels of programmed cell death-1 (PD-1) ligand 1 (PD-L1), interferon-gamma (IFN-γ), and transforming growth factor-β (TGF-β) in circulating extracellular vesicles (EVs) and survival in 30 patients with metastatic melanoma treated with first line anti-PD-1 antibodies. Blood samples were collected at baseline and RNA extracted from EVs; the RNA levels of PD-L1, IFN-γ, and TGF-β were analysed by digital droplet PCR (ddPCR). A biomarker-radiomic correlation analysis was performed in a subset of patients.Results: Patients with high TGF-β expression (cut-off fractional abundance [FA] >0.19) at baseline had longer median progression-free survival (8.4 vs. 1.8 months; p = 0.006) and overall survival (17.9 vs. 2.63 months; p = 0.0009). Moreover, radiomic analysis demonstrated that patients with high TGF-β expression at baseline had smaller lesions (2.41 ± 3.27 mL vs. 42.79 ± 101.08 mL, p < 0.001) and higher dissimilarity (12.01 ± 28.23 vs. 5.65 ± 8.4; p = 0.018).Discussion: These results provide evidence that high TGF-β expression in EVs is associated with a better response to immunotherapy. Further investigation on a larger patient population is needed to validate the predictive power of this potential biomarker of response to ICIs.
- Published
- 2024
- Full Text
- View/download PDF