6533b853fe1ef96bd12ac2f4

RESEARCH PRODUCT

Circulating programmed death ligand-1 (cPD-L1) in non-smallcell lung cancer (NSCLC)

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// Silvia Vecchiarelli 1, * , Francesco Passiglia 2, * , Armida D’Incecco 3, * , Marianna Gallo 4 , Antonella De Luca 4 , Elisa Rossi 5 , Federica D’Inca 1 , Gabriele Minuti 1 , Lorenza Landi 1 , Chiara Bennati 1 , Michela Spreafico 1 , Manolo D’Arcangelo 1 , Valentina Mazza 1 , Nicola Normanno 4 and Federico Cappuzzo 1 1 Department of Oncology and Hematology, AUSL della Romagna, Ravenna, Italy 2 Department of Surgical, Oncological and Stomatological Disciplines, University of Palermo, Palermo, Italy 3 Medical Oncology and Immunotherapy, University Hospital of Siena, Siena, Italy 4 Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori "Fondazione G Pascale"-IRCCS, Naples, Italy 5 Fondazione Ricerca Traslazionale, Rome, Italy * These authors contributed equally to this work Correspondence to: Federico Cappuzzo, email: federico.cappuzzo@auslromagna.it Keywords: PD-L1; immunotherapy; biomarkers; non-small-cell lung cancer Received: November 28, 2017      Accepted: February 27, 2018      Published: April 03, 2018 ABSTRACT Background: This study aimed at investigating feasibility of programmed death ligand-1 (PD-L1) testing in plasma samples of advanced NSCLC patients receiving first-line treatment, assessing whether circulating (c)PD-L1 levels were modified by the therapy and whether baseline cPD-L1 levels were associated with patients’ clinical responses and survival outcome. Methods: Peripheral blood samples were collected from 16 healthy volunteers and 56 newly diagnosed NSCLC patients before and at 12th week during the course of first-line therapy. The level of PD-L1 was measured in plasma samples using the human (PD-L1/CD274) ELISA kit (CUSABIO, MD, USA). The Mann Whitney test or Fisher’s test were used for comparisons. Survival analysis was performed using Kaplan Meyer method, providing median and p -value. Results: Baseline median cPD-L1 was 42.21 pg/ml (range 12.00-143.49) in NSCLC patients and 37.81 pg/ml (range 9.73-90.21) in healthy control cohort ( p = 0.78). Median cPD-L1 increased in patients treated with first-line chemotherapy (63.20 pg/ml vs 39.34 pg/ml; p = 0.002), with no changes in patients exposed to non-chemotherapy drugs (42.39 pg/ml vs 50.67 pg/ml; p = 0.398). Time to progression and overall survival were 4.4 vs 6.9 months ( p = 0.062) and 8.8 vs 9.3 months ( p = 0.216) in cPD-L1 positive vs cPD-L1 negative patients. Baseline cPD-L1 levels increased with the ascending number of metastatic sites, even if the association was not statistically significant ( p = 0.063). Conclusions: This study showed that cPD-L1 testing is feasible, with chemotherapy influencing PD-L1 plasma levels. The possibility of using such test for predicting or monitoring the effect of immunotherapy or combination of chemotherapy and immunotherapy warrant further investigations.