title: Monitoring PD-L1 positive circulating tumor cells in non-small cell lung cancer patients treated with the PD-1 inhibitor Nivolumab.
abstract: Controversial 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.
authors.affiliation: Department of Molecular Medicine, Circulating tumor cells Unit, Sapienza University of Rome.
authors.forename: Chiara
authors.initials: C
authors.lastname: Nicolazzo
authors.affiliation: Department of Molecular Medicine, Circulating tumor cells Unit, Sapienza University of Rome.
authors.forename: Cristina
authors.initials: C
authors.lastname: Raimondi
authors.affiliation: Department of Radiological, Oncological and Pathological Sciences, Division of Medical Oncology, Sapienza University of Rome.
authors.forename: MariaLaura
authors.initials: M
authors.lastname: Mancini
authors.affiliation: Department of Radiological, Oncological and Pathological Sciences, Division of Medical Oncology, Sapienza University of Rome.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Caponnetto
authors.affiliation: Department of Molecular Medicine, Circulating tumor cells Unit, Sapienza University of Rome.
authors.forename: Angela
authors.initials: A
authors.lastname: Gradilone
authors.affiliation: Department of Molecular Medicine, Circulating tumor cells Unit, Sapienza University of Rome.
authors.forename: Orietta
authors.initials: O
authors.lastname: Gandini
authors.affiliation: Department of Molecular Medicine, Circulating tumor cells Unit, Sapienza University of Rome.
authors.forename: Maria
authors.initials: M
authors.lastname: Mastromartino
authors.affiliation: Department of Radiological, Oncological and Pathological Sciences, Division of Medical Oncology, Sapienza University of Rome.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Del Bene
authors.affiliation: Department of Radiological, Oncological and Pathological Sciences, Division of Medical Oncology, Sapienza University of Rome.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Prete
authors.affiliation: Department of Radiological, Oncological and Pathological Sciences, Division of Medical Oncology, Sapienza University of Rome.
authors.forename: Flavia
authors.initials: F
authors.lastname: Longo
authors.affiliation: Department of Radiological, Oncological and Pathological Sciences, Division of Medical Oncology, Sapienza University of Rome.
authors.forename: Enrico
authors.initials: E
authors.lastname: Cortesi
authors.affiliation: Department of Molecular Medicine, Circulating tumor cells Unit, Sapienza University of Rome.
authors.forename: Paola
authors.initials: P
authors.lastname: Gazzaniga
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D060890:B7-H1 Antigen / Q000097:blood* / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood*; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D000077594:Nivolumab; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D000077594:Nivolumab