Monitoring PD-L1 positive circulating tumor cells in non-small cell lung cancer patients treated with the PD-1 inhibitor Nivolumab

• DOI: 10.1038/srep31726
• Publication Date: 2016-08-24T09:43:55Z
• Authors: Chiara Nicolazzo; Cristina Raimondi; MariaLaura Mancini; Salvatore Caponnetto; Angela Gradilone; Orietta Gandini; Maria Mastromartino; Gabriella del Bene; Alessandra Prete; Flavia Longo; Enrico Cortesi; Paola Gazzaniga
• Keywords: Male; 0301 basic medicine; Lung Neoplasms; Time Factors; Programmed Cell Death 1 Receptor; Antineoplastic Agents; Article; B7-H1 Antigen; 03 medical and health sciences; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Humans; Aged; Neoplasm Staging; Antibodies, Monoclonal; Middle Aged; Neoplastic Cells, Circulating; Prognosis; 3. Good health; Nivolumab; Treatment Outcome; Mutation; Disease Progression; immunotherapy; neoplasms; checkpoint inhibitor; Female

AbstractControversial results on the predictive value of programmed death ligand 1 (PD-L1) status in lung tumor tissue for response to immune checkpoint inhibitors do not allow for any conclusive consideration. Liquid biopsy might allow real-time sampling of patients for PD-L1 through the course of the disease. Twenty-four stage IV NSCLC patients included in the Expanded Access Program with Nivolumab were enrolled. Circulating tumor cells (CTCs) were analyzed by CellSearch with anti-human B7-H1/PD-L1 PE-conjugated antibody. PD-L1 expressing CTCs were assessed at baseline, at 3 and 6 months after starting therapy, and correlated with outcome. At baseline and at 3 months of treatment, the presence of CTCs and the expression of PD-L1 on their surface were found associated to poor patients outcome. Nevertheless, the high frequency of PD-L1 expressing CTCs hampered to discriminate the role of PD-L1 in defining prognosis. Conversely although CTCs were found in all patients 6 months after treatment, at this time patients could be dichotomized into two groups based PD-L1 expression on CTCs. Patients with PD-L1 negative CTCs all obtained a clinical benefit, while patients with PD-L1 (+) CTCs all experienced progressive disease. This suggests that the persistence of PD-L1(+) CTCs might mirror a mechanism of therapy escape.