PD-L1 expression on circulating tumor cells and platelets in patients with metastatic breast cancer

<h4>Background</h4> Immune checkpoint inhibition is effective in several cancers. Expression of programmed death-ligand 1 (PD-L1) on circulating tumor or immune effector cells could provide insights into selection of patients for immune checkpoint inhibition. <h4>Methods</h4>...

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Autores principales:	Elizabeth P. Darga, Emily M. Dolce, Fang Fang, Kelley M. Kidwell, Christina L. Gersch, Steven Kregel, Dafydd G. Thomas, Anoop Gill, Martha E. Brown, Steven Gross, Mark Connelly, Michael Holinstat, Erin F. Cobain, James M. Rae, Daniel F. Hayes, Costanza Paoletti
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/63089b9215d1428799266b1d9644f894
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spelling	oai:doaj.org-article:63089b9215d1428799266b1d9644f8942021-11-25T06:10:57ZPD-L1 expression on circulating tumor cells and platelets in patients with metastatic breast cancer1932-6203https://doaj.org/article/63089b9215d1428799266b1d9644f8942021-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8592410/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4> Immune checkpoint inhibition is effective in several cancers. Expression of programmed death-ligand 1 (PD-L1) on circulating tumor or immune effector cells could provide insights into selection of patients for immune checkpoint inhibition. <h4>Methods</h4> Whole blood was collected at serial timepoints from metastatic breast cancer patients and healthy donors for circulating tumor cell (CTC) and platelet PD-L1 analysis with a phycoerythrin-labeled anti-human PD-L1 monoclonal antibody (Biolegend clone 29E.2A3) using the CellSearch® assay. CTC PD-L1 was considered positive if detected on at least 1% of the cells; platelet PD-L1 was considered positive if ≥100 platelets per CellSearch frame expressed PD-L1. <h4>Results</h4> A total of 207 specimens from 124 metastatic breast cancer patients were collected. 52/124 (42%) samples at timepoint-1 (at or close to time of progressive disease) had ≥5 CTC/7.5ml whole blood. Of those, 21 (40%) had positive CTC PD-L1. In addition, platelet PD-L1 expression was observed in 35/124 (28%) at timepoint-1. Platelet PD-L1 was not detected in more than 70 specimens from 12 healthy donors. Platelet PD-L1 was associated with ≥5 CTC/7.5ml whole blood (p = 0.0002), less likely in patients with higher red blood cell counts (OR = 0.72, p<0.001) and a history of smoking tobacco (OR = 0.76, p<0.001). Platelet PD-L1 staining was not associated with tumor marker status, recent procedures or treatments, platelet-affecting drugs, or CTC PD-L1 expression. <h4>Conclusion</h4> PD-L1 expression was found in metastatic breast cancer patients on both CTC and platelets in an independent fashion. Inter-patient platelet PD-L1 expression was highly heterogeneous suggesting that it is a biological event associated with cancer in some but not all patients. Taken together, our data suggest that CTC and platelet PD-L1 expression could play a role in predicting which patients should receive immune checkpoint inhibition and as a pharmacodynamics biomarker during treatment.Elizabeth P. DargaEmily M. DolceFang FangKelley M. KidwellChristina L. GerschSteven KregelDafydd G. ThomasAnoop GillMartha E. BrownSteven GrossMark ConnellyMichael HolinstatErin F. CobainJames M. RaeDaniel F. HayesCostanza PaolettiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elizabeth P. Darga Emily M. Dolce Fang Fang Kelley M. Kidwell Christina L. Gersch Steven Kregel Dafydd G. Thomas Anoop Gill Martha E. Brown Steven Gross Mark Connelly Michael Holinstat Erin F. Cobain James M. Rae Daniel F. Hayes Costanza Paoletti PD-L1 expression on circulating tumor cells and platelets in patients with metastatic breast cancer
description	<h4>Background</h4> Immune checkpoint inhibition is effective in several cancers. Expression of programmed death-ligand 1 (PD-L1) on circulating tumor or immune effector cells could provide insights into selection of patients for immune checkpoint inhibition. <h4>Methods</h4> Whole blood was collected at serial timepoints from metastatic breast cancer patients and healthy donors for circulating tumor cell (CTC) and platelet PD-L1 analysis with a phycoerythrin-labeled anti-human PD-L1 monoclonal antibody (Biolegend clone 29E.2A3) using the CellSearch® assay. CTC PD-L1 was considered positive if detected on at least 1% of the cells; platelet PD-L1 was considered positive if ≥100 platelets per CellSearch frame expressed PD-L1. <h4>Results</h4> A total of 207 specimens from 124 metastatic breast cancer patients were collected. 52/124 (42%) samples at timepoint-1 (at or close to time of progressive disease) had ≥5 CTC/7.5ml whole blood. Of those, 21 (40%) had positive CTC PD-L1. In addition, platelet PD-L1 expression was observed in 35/124 (28%) at timepoint-1. Platelet PD-L1 was not detected in more than 70 specimens from 12 healthy donors. Platelet PD-L1 was associated with ≥5 CTC/7.5ml whole blood (p = 0.0002), less likely in patients with higher red blood cell counts (OR = 0.72, p<0.001) and a history of smoking tobacco (OR = 0.76, p<0.001). Platelet PD-L1 staining was not associated with tumor marker status, recent procedures or treatments, platelet-affecting drugs, or CTC PD-L1 expression. <h4>Conclusion</h4> PD-L1 expression was found in metastatic breast cancer patients on both CTC and platelets in an independent fashion. Inter-patient platelet PD-L1 expression was highly heterogeneous suggesting that it is a biological event associated with cancer in some but not all patients. Taken together, our data suggest that CTC and platelet PD-L1 expression could play a role in predicting which patients should receive immune checkpoint inhibition and as a pharmacodynamics biomarker during treatment.
format	article
author	Elizabeth P. Darga Emily M. Dolce Fang Fang Kelley M. Kidwell Christina L. Gersch Steven Kregel Dafydd G. Thomas Anoop Gill Martha E. Brown Steven Gross Mark Connelly Michael Holinstat Erin F. Cobain James M. Rae Daniel F. Hayes Costanza Paoletti
author_facet	Elizabeth P. Darga Emily M. Dolce Fang Fang Kelley M. Kidwell Christina L. Gersch Steven Kregel Dafydd G. Thomas Anoop Gill Martha E. Brown Steven Gross Mark Connelly Michael Holinstat Erin F. Cobain James M. Rae Daniel F. Hayes Costanza Paoletti
author_sort	Elizabeth P. Darga
title	PD-L1 expression on circulating tumor cells and platelets in patients with metastatic breast cancer
title_short	PD-L1 expression on circulating tumor cells and platelets in patients with metastatic breast cancer
title_full	PD-L1 expression on circulating tumor cells and platelets in patients with metastatic breast cancer
title_fullStr	PD-L1 expression on circulating tumor cells and platelets in patients with metastatic breast cancer
title_full_unstemmed	PD-L1 expression on circulating tumor cells and platelets in patients with metastatic breast cancer
title_sort	pd-l1 expression on circulating tumor cells and platelets in patients with metastatic breast cancer
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/63089b9215d1428799266b1d9644f894
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PD-L1 expression on circulating tumor cells and platelets in patients with metastatic breast cancer

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