Role of plasma exosomes in crosstalk between immune system and hereditary ovarian cancer: Opportunity or challenge?

BackgroundOvarian cancer (OC) is a prevalent gynaecological malignancy characterized by high mortality and low overall survival rates. About 15% of patients harbours germline BRCA1/2 mutations which predispose them to hereditary cancer forms. Specific tumour-derived extracellular vesicles, called exosomes, are considered as potential key players in cross-talk between immune system and tumour microenvironment in several solid tumours. In fact, exosomes play a crucial role in intercellular communication, by transporting biologically active molecules such as DNA, mRNA, miRNA, proteins, lipids, and enzymes. Since scientific evidence highlighted a correlation between BRCA1/2 mutational status, immunogenicity and survival in OC, our study aims to understand whether the exosomes can be used in clinical practice as a source/vehicle of biomarkers able to predict survival in OC women.MethodsExosomes were isolated from plasma collected from 120 metastatic OC patients before surgery and therapy, consecutively enrolled from March 2021 to February 2024 at the University Hospital Policlinico “P. Giaccone� of Palermo (Italy), in order to measure the concentrations of some immunomodulatory molecules, such as PD-1, PD-L1, BTN3A, BTN2A1 and BTLA. All patients were genetically tested for germline BRCA1/2 mutations by next-generation sequencing analysis.ResultsThe mutational screening showed that 20% of patients were carriers of an inherited BRCA mutation (61.3% in BRCA1 and 38.7% in BRCA2), with a median progression-free survival (PFS) longer in women without mutation. Germline BRCA1/2 mutation carriers, with absence of basal peritoneal carcinomatosis, normal body mass index (18.5≥BMI<25) and exosomal concentrations of butyrophilin sub-family 3 member A1 ≤4.75 ng/mL showed a longer PFS (≥30 months) and better prognosis compared to BRCA-wild-type OC women.ConclusionsThis emerging research data suggests that exosomes could serve as carriers of prognostic biomarkers with immunomodulatory functions, and as potential targets for future therapeutic strategies aimed at eliciting antitumor immune responses in inherited OC.Legal entity responsible for the studySiciliAn MicronanOTecH Research and Innovation CEnter “SAMOTHRACE� (MUR, PNRR-M4C2, ECS_00000022), spoke 3: Università degli Studi di Palermo, “S2-COMMs - Micro and Nanotechnologies for Smart & Sustainable Communities�.FundingSiciliAn MicronanOTecH Research and Innovation CEnter “SAMOTHRACE� (MUR, PNRR-M4C2, ECS_00000022).DisclosureAll authors have declared no conflicts of interest.