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

Abstract

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.

• Authors: 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
• Journal: PloS one (PLoS One) Vol. 16 Issue 11 Pg. e0260124 ( 2021) ISSN: 1932-6203 [Electronic] United States
• PMID: 34780566 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• B7-H1 Antigen
• CD274 protein, human

Topics

• B7-H1 Antigen (genetics, metabolism)
• Blood Platelets (metabolism)
• Breast Neoplasms (genetics, metabolism)
• Case-Control Studies
• Cell Line, Tumor
• Female
• Gene Expression Regulation, Neoplastic
• Gene Knockdown Techniques
• Humans
• MCF-7 Cells
• Neoplasm Metastasis
• Neoplastic Cells, Circulating (metabolism)
• Up-Regulation