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Cancers (Basel). 2019 Jun 17;11(6). pii: E835. doi: 10.3390/cancers11060835.

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

Author information

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. m.janning@uke.de.
2
Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. m.janning@uke.de.
3
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. francakobus@yahoo.de.
4
Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. francakobus@yahoo.de.
5
Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. a.babayan@uke.de.
6
Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. h.wikman@uke.de.
7
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. j.velthaus@uke.de.
8
Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. j.velthaus@uke.de.
9
Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. so.bergmann@uke.de.
10
Institute of Hematopathology Hamburg HpH, 22547 Hamburg, Germany. schatz@hp-hamburg.de.
11
Institute of Hematopathology Hamburg HpH, 22547 Hamburg, Germany. falk@hp-hamburg.de.
12
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. LarsArne.Berger@hopa.de.
13
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. lisamarie.boettcher@googlemail.com.
14
Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. lisamarie.boettcher@googlemail.com.
15
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. s.paesler@uke.de.
16
Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. s.paesler@uke.de.
17
Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. tobias.gorges@astrazeneca.com.
18
Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. linda.scarrott@boehringer-ingelheim.com.
19
Boehringer Ingelheim Pharma GmbH & Co. KG, 88397 Biberach, Germany. linda.scarrott@boehringer-ingelheim.com.
20
Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. c.hille@uke.de.
21
Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. s.joosse@uke.de.
22
Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. r.simon@uke.de.
23
Institute of Hematopathology Hamburg HpH, 22547 Hamburg, Germany. mtiemann@hp-hamburg.de.
24
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. c.bokemeyer@uke.de.
25
Lung Clinic Grosshansdorf, Airway Research Center North, German Center of Lung Research, 22927 Grosshansdorf, Germany. M.Reck@lungenclinic.de.
26
Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. s.riethdorf@uke.de.
27
Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. pantel@uke.de.
28
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. s.loges@uke.de.
29
Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. s.loges@uke.de.

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-L1-CTCs, and only 7% displayed exclusively PD-L1-CTCs. 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.

KEYWORDS:

NSCLC; PD-1/PD-L1 inhibition; circulating tumor cells; resistance

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