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>Wh...
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oai:doaj.org-article:28fe13df1c2442cbb060d80eb7cf2b442021-12-02T20:13:03ZPD-L1 expression on circulating tumor cells and platelets in patients with metastatic breast cancer.1932-620310.1371/journal.pone.0260124https://doaj.org/article/28fe13df1c2442cbb060d80eb7cf2b442021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0260124https://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, p e0260124 (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/28fe13df1c2442cbb060d80eb7cf2b44 |
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