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Determination of PD-L1 Expression in Circulating Tumor Cells of NSCLC Patients and Correlation with Response to PD-1/PD-L1 Inhibitors

1
Department of Oncology, Hematology and Bone Marrow Transplantation with section Pneumology, Hubertus Wald University Comprehensive Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
2
Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
3
Institute of Hematopathology Hamburg HpH, 22547 Hamburg, Germany
4
Boehringer Ingelheim Pharma GmbH & Co. KG, 88397 Biberach, Germany
5
Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
6
Lung Clinic Grosshansdorf, Airway Research Center North, German Center of Lung Research, 22927 Grosshansdorf, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Current address: AstraZeneca GmbH, 22880 Wedel, Germany.
Cancers 2019, 11(6), 835; https://doi.org/10.3390/cancers11060835
Received: 27 May 2019 / Revised: 11 June 2019 / Accepted: 12 June 2019 / Published: 17 June 2019
(This article belongs to the Special Issue Liquid Biopsy for Cancer)
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Abstract

Circulating tumor cells (CTCs) hold great potential to answer key questions of how non-small cell lung cancer (NSCLC) evolves and develops resistance upon anti-PD-1/PD-L1 treatment. Currently, their clinical utility in NSCLC is compromised by a low detection rate with the established, Food and Drug Administration (FDA)-approved, EpCAM-based CellSearch® System. We tested an epitope-independent method (ParsortixTM system) and utilized it to assess PD-L1 expression of CTCs from NSCLC patients. We prospectively collected 127 samples, 97 of which were analyzed with the epitope-independent system in comparison to the CellSearch system. CTCs were determined by immunocytochemistry as intact, nucleated, CD45, pankeratins (K)+ cells. PD-L1 status of CTCs was evaluated from 89 samples. With the epitope-independent system, ≥1 CTC per blood sample was detected in 59 samples (61%) compared to 31 samples (32%) with the EpCAM-based system. Upon PD-L1 staining, 47% of patients harbored only PD-L1+CTCs, 47% had PD-L1+ and PD-L1CTCs, and only 7% displayed exclusively PD-L1CTCs. The percentage of PD-L1+CTCs did not correlate with the percentage of PD-L1+ in biopsies determined by immunohistochemistry (p = 0.179). Upon disease progression, all patients showed an increase in PD-L1+CTCs, while no change or a decrease in PD-L1+CTCs was observed in responding patients (n = 11; p = 0.001). Our data show a considerable heterogeneity in the PD-L1 status of CTCs from NSCLC patients. An increase of PD-L1+CTCs holds potential to predict resistance to PD-1/PD-L1 inhibitors. View Full-Text
Keywords: NSCLC; circulating tumor cells; PD-1/PD-L1 inhibition; resistance NSCLC; circulating tumor cells; PD-1/PD-L1 inhibition; resistance
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Janning, M.; Kobus, F.; Babayan, A.; Wikman, H.; Velthaus, J.-L.; Bergmann, S.; Schatz, S.; Falk, M.; Berger, L.-A.; Böttcher, L.-M.; Päsler, S.; Gorges, T.M.; O’Flaherty, L.; Hille, C.; Joosse, S.A.; Simon, R.; Tiemann, M.; Bokemeyer, C.; Reck, M.; Riethdorf, S.; Pantel, K.; Loges, S. Determination of PD-L1 Expression in Circulating Tumor Cells of NSCLC Patients and Correlation with Response to PD-1/PD-L1 Inhibitors. Cancers 2019, 11, 835.

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