{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T01:55:21Z","timestamp":1790906121196,"version":"4.1.0"},"reference-count":51,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2019,6,17]],"date-time":"2019-06-17T00:00:00Z","timestamp":1560729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["LO1863\/4-1"],"award-info":[{"award-number":["LO1863\/4-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Margarete Clemens Stiftung","award":["Margarete Clemens Stiftung"],"award-info":[{"award-number":["Margarete Clemens Stiftung"]}]},{"name":"CancerID","award":["an Innovative Medicines Initiative Joint Undertaking under grant agreement n\u00b0 115749, resources of which are composed of financial contribution from the European Union\u2019s Seventh Framework Program (FP7\/2007-2013) and EFPIA companies\u2019 in kind contribution"],"award-info":[{"award-number":["an Innovative Medicines Initiative Joint Undertaking under grant agreement n\u00b0 115749, resources of which are composed of financial contribution from the European Union\u2019s Seventh Framework Program (FP7\/2007-2013) and EFPIA companies\u2019 in kind contribution"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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\u00ae 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\u2212, pankeratins (K)+ cells. PD-L1 status of CTCs was evaluated from 89 samples. With the epitope-independent system, \u22651 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\u2212CTCs, and only 7% displayed exclusively PD-L1\u2212CTCs. 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.<\/jats:p>","DOI":"10.3390\/cancers11060835","type":"journal-article","created":{"date-parts":[[2019,6,17]],"date-time":"2019-06-17T11:24:45Z","timestamp":1560770685000},"page":"835","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":134,"title":["Determination of PD-L1 Expression in Circulating Tumor Cells of NSCLC Patients and Correlation with Response to PD-1\/PD-L1 Inhibitors"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6632-8506","authenticated-orcid":false,"given":"Melanie","family":"Janning","sequence":"first","affiliation":[{"name":"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"},{"name":"Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franca","family":"Kobus","sequence":"additional","affiliation":[{"name":"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"},{"name":"Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Babayan","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6862-0888","authenticated-orcid":false,"given":"Harriet","family":"Wikman","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janna-Lisa","family":"Velthaus","sequence":"additional","affiliation":[{"name":"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"},{"name":"Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Bergmann","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2811-3667","authenticated-orcid":false,"given":"Stefanie","family":"Schatz","sequence":"additional","affiliation":[{"name":"Institute of Hematopathology Hamburg HpH, 22547 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Falk","sequence":"additional","affiliation":[{"name":"Institute of Hematopathology Hamburg HpH, 22547 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars-Arne","family":"Berger","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa-Marie","family":"B\u00f6ttcher","sequence":"additional","affiliation":[{"name":"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"},{"name":"Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarina","family":"P\u00e4sler","sequence":"additional","affiliation":[{"name":"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"},{"name":"Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias M.","family":"Gorges","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"O\u2019Flaherty","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"},{"name":"Boehringer Ingelheim Pharma GmbH &amp; Co. KG, 88397 Biberach, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Hille","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4296-5615","authenticated-orcid":false,"given":"Simon A.","family":"Joosse","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0158-4258","authenticated-orcid":false,"given":"Ronald","family":"Simon","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Tiemann","sequence":"additional","affiliation":[{"name":"Institute of Hematopathology Hamburg HpH, 22547 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Bokemeyer","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Reck","sequence":"additional","affiliation":[{"name":"Lung Clinic Grosshansdorf, Airway Research Center North, German Center of Lung Research, 22927 Grosshansdorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Riethdorf","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5736-2772","authenticated-orcid":false,"given":"Klaus","family":"Pantel","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Loges","sequence":"additional","affiliation":[{"name":"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"},{"name":"Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1056\/NEJMra1703413","article-title":"Precision diagnosis and treatment for advanced non-small-cell lung cancer","volume":"377","author":"Reck","year":"2017","journal-title":"N. 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