Circulating programmed death ligand-1 (cPD-L1) in non-small-cell lung cancer (NSCLC)
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Silvia Vecchiarelli1,*, Francesco Passiglia2,*, Armida D’Incecco3,*, Marianna Gallo4, Antonella De Luca4, Elisa Rossi5, Federica D’Incà1, Gabriele Minuti1, Lorenza Landi1, Chiara Bennati1, Michela Spreafico1, Manolo D’Arcangelo1, Valentina Mazza1, Nicola Normanno4 and Federico Cappuzzo1
1Department of Oncology and Hematology, AUSL della Romagna, Ravenna, Italy
2Department of Surgical, Oncological and Stomatological Disciplines, University of Palermo, Palermo, Italy
3Medical Oncology and Immunotherapy, University Hospital of Siena, Siena, Italy
4Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori "Fondazione G Pascale"-IRCCS, Naples, Italy
5Fondazione Ricerca Traslazionale, Rome, Italy
*These authors contributed equally to this work
Federico Cappuzzo, email: firstname.lastname@example.org
Keywords: PD-L1; immunotherapy; biomarkers; non-small-cell lung cancer
Received: November 28, 2017 Accepted: February 27, 2018 Published: April 03, 2018
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.
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