PD-L1 expression on circulating tumor cells and platelets in patients with metastatic breast cancer
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
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| Enthalten in: |
PloS one - 16(2021), 11 vom: 15., Seite e0260124 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Darga, Elizabeth P [VerfasserIn] |
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| Links: |
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| Themen: |
B7-H1 Antigen |
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| Anmerkungen: |
Date Completed 29.12.2021 Date Revised 29.12.2021 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.1371/journal.pone.0260124 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM333183134 |
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| 100 | 1 | |a Darga, Elizabeth P |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a PD-L1 expression on circulating tumor cells and platelets in patients with metastatic breast cancer |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 29.12.2021 | ||
| 500 | |a Date Revised 29.12.2021 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: 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 | ||
| 520 | |a METHODS: 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 | ||
| 520 | |a RESULTS: 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 | ||
| 520 | |a CONCLUSION: 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
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| 700 | 1 | |a Dolce, Emily M |e verfasserin |4 aut | |
| 700 | 1 | |a Fang, Fang |e verfasserin |4 aut | |
| 700 | 1 | |a Kidwell, Kelley M |e verfasserin |4 aut | |
| 700 | 1 | |a Gersch, Christina L |e verfasserin |4 aut | |
| 700 | 1 | |a Kregel, Steven |e verfasserin |4 aut | |
| 700 | 1 | |a Thomas, Dafydd G |e verfasserin |4 aut | |
| 700 | 1 | |a Gill, Anoop |e verfasserin |4 aut | |
| 700 | 1 | |a Brown, Martha E |e verfasserin |4 aut | |
| 700 | 1 | |a Gross, Steven |e verfasserin |4 aut | |
| 700 | 1 | |a Connelly, Mark |e verfasserin |4 aut | |
| 700 | 1 | |a Holinstat, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Cobain, Erin F |e verfasserin |4 aut | |
| 700 | 1 | |a Rae, James M |e verfasserin |4 aut | |
| 700 | 1 | |a Hayes, Daniel F |e verfasserin |4 aut | |
| 700 | 1 | |a Paoletti, Costanza |e verfasserin |4 aut | |
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