Heterogeneous Expression of Programmed Death Receptor-ligand 1 on Circulating Tumor Cells in Patients With Lung Cancer.
BACKGROUND
Blockade of the programmed death receptor-1 (PD-1) pathway is effective against solid tumors including lung cancer. PD-ligand 1 (PD-L1) expression on tumor tissue serves as a predictive biomarker for the efficacy of PD-1 pathway blockade. Here, we evaluated the expression of PD-L1 on circulating tumor cells (CTCs) in patients with lung cancer.


MATERIALS AND METHODS
Peripheral whole blood (3 mL) was collected from patients, and CTCs and PD-L1 expression were detected using a microcavity array (MCA) system. Immunohistochemistry for PD-L1 detection was also performed using matched tumor tissues.


RESULTS
Sixty-seven patients with lung cancer were enrolled in the study between July 2015 and April 2016 at Wakayama Medical University Hospital. The characteristics of the patients were as follows: median age, 71 years (range, 39-86 years); male, 72%; stage II to III/IV, 14%/85%; non-small-cell lung cancer/small-cell lung cancer/other, 73%/21%/6%. CTCs were detected in 66 of 67 patients (median, 19; range, 0-115), and more than 5 CTCs were detected in 78% of patients. PD-L1-expressing CTCs were detected in 73% of patients, and the proportion score of PD-L1-expressing CTCs ranged from 3% to 100%, suggesting intra-patient heterogeneity of PD-L1 expression on CTCs. Tumor tissues were available from 27 patients and were immunostained for PD-L1, and no correlation was observed between tumor tissues and CTCs based on the proportion score (R2 = 0.0103).


CONCLUSION
PD-L1 expression was detectable on CTCs in patients with lung cancer, and intra-patient heterogeneity was observed. No correlation was observed between PD-L1 expression in tumor tissues and CTCs.
['Koh|Yasuhiro|Y|', 'Yagi|Satomi|S|', 'Akamatsu|Hiroaki|H|', 'Kanai|Kuninobu|K|', 'Hayata|Atsushi|A|', 'Tokudome|Nahomi|N|', 'Akamatsu|Keiichiro|K|', 'Higuchi|Masayuki|M|', 'Kanbara|Hisashige|H|', 'Nakanishi|Masanori|M|', 'Ueda|Hiroki|H|', 'Yamamoto|Nobuyuki|N|']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D000074322:Antineoplastic Agents, Immunological D060890:B7-H1 Antigen D054316:Biomarkers, Pharmacological D002289:Carcinoma, Non-Small-Cell Lung D005260:Female D006801:Humans D007150:Immunohistochemistry D008175:Lung Neoplasms D008297:Male D008875:Middle Aged D009367:Neoplasm Staging D009360:Neoplastic Cells, Circulating D018579:Patient Selection D061026:Programmed Cell Death 1 Receptor
Immune checkpoint inhibitors Liquid biopsy Noninvasive diagnostics Precision medicine Tumor heterogeneity