de Miguel-Perez, DiegoRusso, AlessandroArrieta, OscarAk, MuratBarron, FelicianoGunasekaran, MuthukumarMamindla, PriyadarshiniLara-Mejia, LuisPeterson, Christine BEr, Mehmet EPeddagangireddy, VishalBuemi, FrancescoCooper, BrandonManca, PaoloLapidus, Rena GHsia, Ru-ChingCardona, Andres FNaing, AungKaushal, SunjayHirsch, Fred RMack, Philip CSerrano, Maria JoseAdamo, VincenzoColen, Rivka RRolfo, Christian2023-05-032023-05-032022-06-02http://hdl.handle.net/10668/20349Immune-checkpoint inhibitors (ICIs) changed the therapeutic landscape of patients with lung cancer. However, only a subset of them derived clinical benefit and evidenced the need to identify reliable predictive biomarkers. Liquid biopsy is the non-invasive and repeatable analysis of biological material in body fluids and a promising tool for cancer biomarkers discovery. In particular, there is growing evidence that extracellular vesicles (EVs) play an important role in tumor progression and in tumor-immune interactions. Thus, we evaluated whether extracellular vesicle PD-L1 expression could be used as a biomarker for prediction of durable treatment response and survival in patients with non-small cell lung cancer (NSCLC) undergoing treatment with ICIs. Dynamic changes in EV PD-L1 were analyzed in plasma samples collected before and at 9 ± 1 weeks during treatment in a retrospective and a prospective independent cohorts of 33 and 39 patients, respectively. As a result, an increase in EV PD-L1 was observed in non-responders in comparison to responders and was an independent biomarker for shorter progression-free survival and overall survival. To the contrary, tissue PD-L1 expression, the commonly used biomarker, was not predictive neither for durable response nor survival. These findings indicate that EV PD-L1 dynamics could be used to stratify patients with advanced NSCLC who would experience durable benefit from ICIs.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/BiomarkersExtracellular vesiclesImmunotherapyNSCLCPD-L1B7-H1 AntigenCarcinoma, Non-Small-Cell LungExtracellular VesiclesHumansImmune Checkpoint InhibitorsLung NeoplasmsProspective StudiesRetrospective Studiesresearch article35650597open access10.1186/s13046-022-02379-11756-9966PMC9161571https://doi.org/10.1186/s13046-022-02379-1https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9161571/pdf