PD-L1 mRNA expression in plasma-derived exosomes is associated with response to anti-PD-1 antibodies in melanoma and NSCLC

Background: PD-L1 expression in tumour tissues is widely used to select patients to receive anti-PD-1/PD-L1 antibodies but data are lacking on the correlation of plasma PD-L1 levels with the effect of treatments. Methods: To investigate the association between PD-L1 mRNA in plasma-derived exosomes and response to nivolumab and pembrolizumab in patients with melanoma (n=18) and NSCLC (n=8), blood was obtained at time point 0 and after 2 months. Exosomal PD-L1 mRNA was measured by digital droplet PCR. Results: The mean±s.e.m. PD-L1 levels in patients with complete and partial responses were 830.4±231.3 and 242.5±82.5 copies per ml at time 0 vs 2 months, respectively (P=0.016). In patients with stable disease the mean±s.e.m. values were 298.8±97.2 vs 247.5±29.8 copies per ml (P=0.586), while in progressive disease, PD-L1 mRNA levels were 204.0±68.8 vs 416.0±87.8 copies per ml at time 0 vs 2 months, respectively (P=0.001). Conclusions: This study demonstrates that exosomal PD-L1 is significantly associated with response to treatment.