Research Papers:

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

Silvia Vecchiarelli, Francesco Passiglia, Armida D’Incecco, Marianna Gallo, Antonella De Luca, Elisa Rossi, Federica D’Incà, Gabriele Minuti, Lorenza Landi, Chiara Bennati, Michela Spreafico, Manolo D’Arcangelo, Valentina Mazza, Nicola Normanno and Federico Cappuzzo _

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Oncotarget. 2018; 9:17554-17563. https://doi.org/10.18632/oncotarget.24785

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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

Correspondence to:

Federico Cappuzzo, email: [email protected]

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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