Thesis etd-12222022-094455 |
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Thesis type
Tesi di specializzazione (5 anni)
Author
MANACORDA, SIMONA
URN
etd-12222022-094455
Thesis title
TGF-β mRNA levels in circulating extracellular vesicles are associated with response to anti-PD1 treatment in metastatic melanoma
Department
RICERCA TRASLAZIONALE E DELLE NUOVE TECNOLOGIE IN MEDICINA E CHIRURGIA
Course of study
ONCOLOGIA MEDICA
Supervisors
relatore Prof.ssa Cremolini, Chiara
correlatore Dott. Marconcini, Riccardo
correlatore Dott. Marconcini, Riccardo
Keywords
- anti-PD1
- EVs
- Immunotherapy
- Melanoma
- TGF- β
Graduation session start date
10/01/2023
Availability
Withheld
Release date
10/01/2093
Summary
Background: Immune checkpoint inhibitors (ICIs) represent one of the standard therapies for metastatic malignant melanoma. However, a number of patients do not respond to ICIs and biomarker development remains challenging.
Methods: This single cohort of observational 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 vescicles (EVs) in 29 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).
Results: Patients with high TGF-β expression (cut-off fractional abundance [FA] >0.17) at baseline had longer median progression-free survival (9.5 vs. 2.1 months; p=0.0172) and overall survival (17.9 vs 2.4 months; p=0.0104).
Conclusions: These results provide evidence that high TGF-β expression in EVs at baseline 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.
Methods: This single cohort of observational 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 vescicles (EVs) in 29 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).
Results: Patients with high TGF-β expression (cut-off fractional abundance [FA] >0.17) at baseline had longer median progression-free survival (9.5 vs. 2.1 months; p=0.0172) and overall survival (17.9 vs 2.4 months; p=0.0104).
Conclusions: These results provide evidence that high TGF-β expression in EVs at baseline 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.
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