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

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, and Costanza Paoletti

Subjects
Medicine, Science
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, pConclusion 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.

Published
2021

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

Author

Fang Fang, Erin F. Cobain, Martha E. Brown, Daniel F. Hayes, Emily M. Dolce, Michael Holinstat, Elizabeth P. Darga, Costanza Paoletti, Kelley M. Kidwell, James M. Rae, Anoop Gill, Steven Kregel, Steven P. Gross, Mark Connelly, Dafydd G. Thomas, and Christina L. Gersch

Subjects
Physiology, Cancer Treatment, Biochemistry, B7-H1 Antigen, Metastasis, Circulating tumor cell, Animal Cells, Breast Tumors, Basic Cancer Research, Medicine and Health Sciences, Medicine, Neoplasm Metastasis, Whole blood, Staining, Multidisciplinary, Cell Staining, Small interfering RNA, Neoplastic Cells, Circulating, Metastatic breast cancer, Body Fluids, Up-Regulation, Nucleic acids, Gene Expression Regulation, Neoplastic, Blood, Oncology, Gene Knockdown Techniques, MCF-7 Cells, Female, Anatomy, Cellular Types, Research Article, Platelets, Blood Platelets, Science, Breast Neoplasms, Research and Analysis Methods, Breast cancer, Cell Line, Tumor, Breast Cancer, Genetics, Humans, Non-coding RNA, Tumor marker, Blood Cells, business.industry, DAPI staining, Cancer, Biology and Life Sciences, Cancers and Neoplasms, Cell Biology, medicine.disease, Immune checkpoint, Gene regulation, Specimen Preparation and Treatment, Case-Control Studies, Nuclear staining, Cancer research, RNA, Gene expression, business
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 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.

Published
2021

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