Circulating PD-L1-exosomes to monitor tumor response in melanoma patients.

Abstract

9517 Background: In the era of effective molecular targeted treatments and immunotherapies, there is an urgent need to implement the use of circulating biomarkers in the clinic to facilitate personalized therapy and predict treatment response. We conducted a retrospective study to demonstrate the involvement of circulating PD-L1 exosomes in melanoma patients. Methods: One hundred melanoma patients were included. Exosomes were isolated by ultracentrifugation and evaluated by nanoparticle tracking analysis using a NS300 Instrument (Nanosight, Amesbury, UK). Isolated exosomes were tested for the expression of exosomes markers such as TSG101. PD-L1 expression in plasma and in melanoma plasma-derived exosomes (ExoPD-L1) was measured using an enzyme-linked immunosorbent assay (PD-L1 Human ELISA Kit, Invitrogen). Results: First, ExoPD-L1 was assessed in melanoma cell lines. Exosomes may have a role in cancer immunosuppression mediated by T-cells since they were as efficient as cancer cells to inhibit T-cells activation. In melanoma patients, ExoPD-L1 (median 64,26 pg/mL) was significantly higher than free PD-L1 in the plasma which was barely detectable (0,1 pg/mL). Furthermore, ExoPD-L1 was detected in all patients whereas only 67 % were PD-L1 positive in tumor. Although baseline ExoPD-L1 levels were not associated with clinicopathologic characteristics and tumour burden, ExoPD-L1 variations (ΔExoPD-L1) after treatment correlated with tumor response and survival. A ΔExoPD-L1 cut-off of > 100 was defined, yielding a 83% sensitivity, a 70% specificity, a 91% positive predictive value and a 54% negative predictive values for disease progression. The use of this cut-off allowed stratification in two groups of patients statistically different in terms of overall survival and progression free survival. Conclusions: PD-L1 level in circulating exosomes may be a more reliable marker than PD-L1 expression in the tumor tissue. Monitoring of circulating exosomal PD-L1 may be a promising biomarker to predict tumor response and correlate with survival.