{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T16:07:14Z","timestamp":1790438834381,"version":"4.1.0"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T00:00:00Z","timestamp":1638144000000},"content-version":"vor","delay-in-days":725,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>PD-1 inhibitors are routinely used for the treatment of advanced melanoma. This study sought to determine whether PD-L1 expression on circulating tumor cells (CTCs) can serve as a predictive biomarker of clinical benefit and response to treatment with the PD-1 inhibitor pembrolizumab.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Blood samples were collected from patients with metastatic melanoma receiving pembrolizumab, prior to treatment and 6\u201312\u2009weeks after initiation of therapy. Multiparametric flow cytometry was used to identify CTCs and evaluate the expression of PD-L1.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>CTCs were detected in 25 of 40 patients (63%). Patients with detectable PD-L1+ CTCs (14\/25, 64%) had significantly longer progression-free survival (PFS) compared with patients with PD-L1\u2212 CTCs (26.6 months vs. 5.5 months; p = .018). The 12-month PFS rates were 76% versus 22% in the PD-L1+ versus PD-L1\u2212 CTCs groups (p = .012), respectively. A multivariate linear regression analysis confirmed that PD-L1+ CTC is an independent predictive biomarker of PFS (hazard ratio, 0.229; 95% confidence interval, 0.052\u20131.012; p = .026).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our results reveal the potential of CTCs as a noninvasive real-time biopsy to evaluate PD-L1 expression in patients with melanoma. PD-L1 expression on CTCs may be predictive of response to pembrolizumab and longer PFS.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1634\/theoncologist.2019-0557","type":"journal-article","created":{"date-parts":[[2019,12,5]],"date-time":"2019-12-05T20:35:13Z","timestamp":1575578113000},"page":"e520-e527","source":"Crossref","is-referenced-by-count":75,"title":["PD-L1 Expression on Circulating Tumor Cells May Be Predictive of Response to Pembrolizumab in Advanced Melanoma: Results from a Pilot Study"],"prefix":"10.1093","volume":"25","author":[{"given":"Muhammad A.","family":"Khattak","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Fiona Stanley Hospital, Australia"},{"name":"School of Medical and Health Sciences, Edith Cowan University, Perth, Australia"},{"name":"Faculty of Health and Medical Sciences, University of Western Australia, Crawley, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Reid","sequence":"additional","affiliation":[{"name":"School of Medical and Health Sciences, Edith Cowan University, Perth, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Freeman","sequence":"additional","affiliation":[{"name":"School of Medical and Health Sciences, Edith Cowan University, Perth, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Pereira","sequence":"additional","affiliation":[{"name":"School of Medical and Health Sciences, Edith Cowan University, Perth, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashleigh","family":"McEvoy","sequence":"additional","affiliation":[{"name":"School of Medical and Health Sciences, Edith Cowan University, Perth, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnny","family":"Lo","sequence":"additional","affiliation":[{"name":"School of Engineering, Edith Cowan University, Joondalup, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus H.","family":"Frank","sequence":"additional","affiliation":[{"name":"School of Medical and Health Sciences, Edith Cowan University, Perth, Australia"},{"name":"Transplantation Research Program, Boston Children's Hospital and Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarek","family":"Meniawy","sequence":"additional","affiliation":[{"name":"Faculty of Health and Medical Sciences, University of Western Australia, Crawley, Australia"},{"name":"Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Didan","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Fiona Stanley Hospital, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac","family":"Spencer","sequence":"additional","affiliation":[{"name":"School of Medical and Health Sciences, Edith Cowan University, Perth, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benhur","family":"Amanuel","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology, PathWest, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Millward","sequence":"additional","affiliation":[{"name":"Faculty of Health and Medical Sciences, University of Western Australia, Crawley, Australia"},{"name":"Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Ziman","sequence":"additional","affiliation":[{"name":"School of Medical and Health Sciences, Edith Cowan University, Perth, Australia"},{"name":"Faculty of Health and Medical Sciences, University of Western Australia, Crawley, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elin","family":"Gray","sequence":"additional","affiliation":[{"name":"School of Medical and Health Sciences, Edith Cowan University, Perth, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,12,5]]},"reference":[{"issue":"suppl 15","key":"2021122510132261600_R1","article-title":"5-year survival outcomes in patients (pts) with advanced melanoma treated with pembrolizumab (pembro) in KEYNOTE-001","volume":"36","author":"Hamid","year":"2018","journal-title":"J Clin Oncol"},{"key":"2021122510132261600_R2","doi-asserted-by":"crossref","first-page":"e542","DOI":"10.1016\/S1470-2045(16)30406-5","article-title":"Predictive biomarkers for checkpoint inhibitor-based immunotherapy","volume":"17","author":"Gibney","year":"2016","journal-title":"Lancet Oncol"},{"key":"2021122510132261600_R3","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.jtho.2016.11.2228","article-title":"PD-L1 immunohistochemistry assays for lung cancer: Results from phase 1 of the Blueprint PD-L1 IHC Assay Comparison Project","volume":"12","author":"Hirsch","year":"2017","journal-title":"J Thorac Oncol"},{"key":"2021122510132261600_R4","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.coph.2015.05.011","article-title":"PD-1\/PD-L1 inhibitors","volume":"23","author":"Sunshine","year":"2015","journal-title":"Curr Opin Pharmacol"},{"key":"2021122510132261600_R5","doi-asserted-by":"crossref","first-page":"4938","DOI":"10.1158\/1078-0432.CCR-16-1821","article-title":"PD-L1 expression in melanoma: A quantitative immunohistochemical antibody comparison","volume":"23","author":"Sunshine","year":"2017","journal-title":"Clin Cancer Res"},{"key":"2021122510132261600_R6","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1111\/imj.12996","article-title":"Liquid biopsies: Advancing cancer research through drops of blood","volume":"46","author":"Khattak","year":"2016","journal-title":"Intern Med J"},{"key":"2021122510132261600_R7","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1056\/NEJMoa1604958","article-title":"Mutations associated with acquired resistance to PD-1 blockade in melanoma","volume":"375","author":"Zaretsky","year":"2016","journal-title":"N Engl J Med"},{"key":"2021122510132261600_R8","doi-asserted-by":"crossref","DOI":"10.1186\/s13148-017-0332-8","article-title":"Aberrant DNA methylation in melanoma: Biomarker and therapeutic opportunities","volume":"9","author":"Micevic","year":"2017","journal-title":"Clin Epigenetics"},{"key":"2021122510132261600_R9","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.trsl.2018.07.003","article-title":"Circulating tumor cells as \u201cliquid biopsies\u201d to understand cancer metastasis","volume":"201","author":"Woo","year":"2018","journal-title":"Transl Res"},{"key":"2021122510132261600_R10","doi-asserted-by":"crossref","DOI":"10.1200\/PO.17.00279","article-title":"Clinical application of circulating tumor cells and circulating tumor DNA in uveal melanoma","author":"Beasley","year":"2018","journal-title":"JCO Precis Oncol"},{"key":"2021122510132261600_R11","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1038\/nm.4239","article-title":"Molecular analysis of circulating tumor cells identifies distinct copy-number profiles in patients with chemosensitive and chemorefractory small-cell lung cancer","volume":"23","author":"Carter","year":"2017","journal-title":"Nat Med"},{"key":"2021122510132261600_R12","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1038\/nm.3600","article-title":"Tumorigenicity and genetic profiling of circulating tumor cells in small-cell lung cancer","volume":"20","author":"Hodgkinson","year":"2014","journal-title":"Nat Med"},{"key":"2021122510132261600_R13","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1038\/jid.2015.127","article-title":"Circulating melanoma cell subpopulations: Their heterogeneity and differential responses to treatment","volume":"135","author":"Gray","year":"2015","journal-title":"J Invest Dermatol"},{"key":"2021122510132261600_R14","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1038\/s41379-018-0173-9","article-title":"Programmed death ligand-1 expression in non-small cell lung cancer in a Western Australian population and correlation with clinicopathologic features","volume":"32","author":"Ye","year":"2019","journal-title":"Mod Pathol"},{"key":"2021122510132261600_R15","doi-asserted-by":"crossref","DOI":"10.1186\/s40364-017-0093-8","article-title":"Utility of PD-L1 immunohistochemistry assays for predicting PD-1\/PD-L1 inhibitor response","volume":"5","author":"Diggs","year":"2017","journal-title":"Biomark Res"},{"key":"2021122510132261600_R16","doi-asserted-by":"crossref","first-page":"S48","DOI":"10.21037\/atm.2018.10.09","article-title":"Non-invasive assessment of tumor PD-L1 status with circulating tumor cells","volume":"6","author":"Ulrich","year":"2018","journal-title":"Ann Transl Med"},{"key":"2021122510132261600_R17","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1093\/annonc\/mdx636","article-title":"Detection of PD-L1 in circulating tumor cells and white blood cells from patients with advanced non-small-cell lung cancer","volume":"29","author":"Ilie","year":"2018","journal-title":"Ann Oncol"},{"key":"2021122510132261600_R18","doi-asserted-by":"crossref","first-page":"67355","DOI":"10.18632\/oncotarget.18641","article-title":"Isolation and detection of circulating tumour cells from metastatic melanoma patients using a slanted spiral microfluidic device","volume":"8","author":"Aya-Bonilla","year":"2017","journal-title":"Oncotarget"},{"key":"2021122510132261600_R19","doi-asserted-by":"crossref","first-page":"157","DOI":"10.3390\/cancers11020157","article-title":"Immunomagnetic-enriched subpopulations of melanoma circulating tumour cells (CTCs) exhibit distinct transcriptome profiles","volume":"11","author":"Aya-Bonilla","year":"2019","journal-title":"Cancers"},{"key":"2021122510132261600_R20","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1038\/jid.2012.468","article-title":"Biomarker utility of circulating tumor cells in metastatic cutaneous melanoma","volume":"133","author":"Khoja","year":"2013","journal-title":"J Invest Dermatol"},{"key":"2021122510132261600_R21","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2407-14-423","article-title":"Monitoring changes in circulating tumour cells as a prognostic indicator of overall survival and treatment response in patients with metastatic melanoma","volume":"14","author":"Klinac","year":"2014","journal-title":"BMC Cancer"},{"key":"2021122510132261600_R22","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1073\/pnas.1719264115","article-title":"Molecular signatures of circulating melanoma cells for monitoring early response to immune checkpoint therapy","volume":"115","author":"Hong","year":"2018","journal-title":"Proc Natl Acad Sci USA"},{"key":"2021122510132261600_R23","doi-asserted-by":"crossref","first-page":"4102","DOI":"10.1200\/JCO.2016.67.2477","article-title":"Programmed death-ligand 1 expression and response to the anti-programmed death 1 antibody pembrolizumab in melanoma","volume":"34","author":"Daud","year":"2016","journal-title":"J Clin Oncol"},{"key":"2021122510132261600_R24","doi-asserted-by":"crossref","first-page":"25265","DOI":"10.18632\/oncotarget.25404","article-title":"Quantitative monitoring of circulating tumor DNA predicts response of cutaneous metastatic melanoma to anti-PD1 immunotherapy","volume":"9","author":"Herbreteau","year":"2018","journal-title":"Oncotarget"},{"key":"2021122510132261600_R25","doi-asserted-by":"crossref","first-page":"42008","DOI":"10.18632\/oncotarget.5788","article-title":"Circulating tumor DNA to monitor treatment response and detect acquired resistance in patients with metastatic melanoma","volume":"6","author":"Gray","year":"2015","journal-title":"Oncotarget"},{"key":"2021122510132261600_R26","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1093\/annonc\/mdx717","article-title":"Circulating tumor DNA predicts survival in patients with resected high-risk stage II\/III melanoma","volume":"29","author":"Lee","year":"2018","journal-title":"Ann Oncol"}],"container-title":["The Oncologist"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1634\/theoncologist.2019-0557","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1634\/theoncologist.2019-0557","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/25\/3\/e520\/41920264\/oncolo_25_3_e520.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/25\/3\/e520\/41920264\/oncolo_25_3_e520.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,25]],"date-time":"2021-12-25T10:15:26Z","timestamp":1640427326000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/oncolo\/article\/25\/3\/e520\/6443635"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,5]]},"references-count":26,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2019,12,5]]},"published-print":{"date-parts":[[2020,3,1]]}},"URL":"https:\/\/doi.org\/10.1634\/theoncologist.2019-0557","relation":{},"ISSN":["1083-7159","1549-490X"],"issn-type":[{"value":"1083-7159","type":"print"},{"value":"1549-490X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,3,1]]},"published":{"date-parts":[[2019,12,5]]}}}