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.