17
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

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

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          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.

          Related collections

          Most cited references42

          • Record: found
          • Abstract: found
          • Article: found

          Hallmarks of Cancer: The Next Generation

          The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list-reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the "tumor microenvironment." Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer. Copyright © 2011 Elsevier Inc. All rights reserved.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer

            Unresectable locally advanced or metastatic triple-negative (hormone-receptor-negative and human epidermal growth factor receptor 2 [HER2]-negative) breast cancer is an aggressive disease with poor outcomes. Nanoparticle albumin-bound (nab)-paclitaxel may enhance the anticancer activity of atezolizumab.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Emerging Biological Principles of Metastasis.

              Metastases account for the great majority of cancer-associated deaths, yet this complex process remains the least understood aspect of cancer biology. As the body of research concerning metastasis continues to grow at a rapid rate, the biological programs that underlie the dissemination and metastatic outgrowth of cancer cells are beginning to come into view. In this review we summarize the cellular and molecular mechanisms involved in metastasis, with a focus on carcinomas where the most is known, and we highlight the general principles of metastasis that have begun to emerge.
                Bookmark

                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: ResourcesRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: MethodologyRole: SoftwareRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: MethodologyRole: ResourcesRole: SoftwareRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: ResourcesRole: VisualizationRole: Writing – review & editing
                Role: InvestigationRole: MethodologyRole: ResourcesRole: Writing – review & editing
                Role: InvestigationRole: ResourcesRole: Writing – review & editing
                Role: ResourcesRole: Writing – review & editing
                Role: ResourcesRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: Writing – review & editing
                Role: ConceptualizationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                15 November 2021
                2021
                : 16
                : 11
                : e0260124
                Affiliations
                [1 ] Breast Oncology Program, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America
                [2 ] University of Michigan Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan, United States of America
                [3 ] Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, Michigan, United States of America
                [4 ] Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, United States of America
                [5 ] Menarini Silicon Biosystems, Huntingdon Valley, Pennsylvania, United States of America
                [6 ] Departments of Pharmacology and Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America
                Universite de Nantes, FRANCE
                Author notes

                Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: C.P. reports non-financial support (travel paid), contracts, and research support from Menarini Silicon Biosystems (MSB), the manufacturer of CellSearch® and, outside the submitted work, research funding from AstraZeneca, and Pfizer. C.P. is currently an employee of Eisai, Inc. University of Michigan (UM) has received funding to support research on behalf of D.F.H. and from Menarini/Silicon Biosystems, manufacturer of CellSearch. UM has submitted a patent application related to CTC and platelet PDL1 testing on which D.F.H., C.P., E.P.D. and E.M.D. are named inventors/co-inventors.UM holds patent US 8,790,878 B2 for which D.F.H. is designated as inventor, and that is licensed to MSB with annual royalties through January 2021. Outside the submitted work D.F.H. holds stock options from InBiomotion, and serves on advisory boards for Cepheid, Freenome, CellWorks, Lexent Bio, EPIC Science, Salutogenic Innovations, L-Nutra, BioVeca, OncoCyte, Turnstone Biologics, Predictus BioSciences, Tempus, Guardant and UM has received funding to support research on behalf of D.F.H. from Astra Zeneca, Merrimack, Eli Lilly, Puma Biotechnology, Pfizer. Outside the submitted work M.H. serves as a consultant and receives research support from Veralox Therapeutics. Outside the submitted work E.F.C. has served advisory/consulting roles for AstraZeneca, Biotheranostics, Ayala Pharmaceuticals and Athenex Oncology. The remaining co-authors have declared that no competing interests exist.

                [¤]

                Current address: EISAI Inc., Woodcliff Lake, New Jersey, United States of America

                Author information
                https://orcid.org/0000-0001-7212-8116
                https://orcid.org/0000-0002-1717-4483
                https://orcid.org/0000-0001-5100-1933
                Article
                PONE-D-21-26910
                10.1371/journal.pone.0260124
                8592410
                34780566
                afe7ebb1-0270-4498-b633-be577f8591f4
                © 2021 Darga et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 19 August 2021
                : 2 November 2021
                Page count
                Figures: 4, Tables: 4, Pages: 19
                Funding
                Funded by: Menarini Silicon Biosystems
                Award Recipient :
                Funded by: the Fashion Footwear Charitable Foundation of New York/QVC Presents Shoes on Sale ™
                Award Recipient :
                Funded by: National Cancer Institute Cancer Center Support Grant
                Award ID: P30CA046592
                This work was supported by Menarini Silicon Biosystems, the Fashion Footwear Charitable Foundation of New York/QVC Presents Shoes on Sale ™ (D.F.H.), and the National Cancer Institute Cancer Center Support Grant (P30CA046592). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Blood
                Platelets
                Medicine and Health Sciences
                Anatomy
                Body Fluids
                Blood
                Platelets
                Biology and Life Sciences
                Physiology
                Body Fluids
                Blood
                Platelets
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Blood Cells
                Platelets
                Research and Analysis Methods
                Specimen Preparation and Treatment
                Staining
                Cell Staining
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Breast Tumors
                Breast Cancer
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Blood
                Medicine and Health Sciences
                Anatomy
                Body Fluids
                Blood
                Biology and Life Sciences
                Physiology
                Body Fluids
                Blood
                Medicine and Health Sciences
                Oncology
                Cancer Treatment
                Medicine and Health Sciences
                Oncology
                Metastasis
                Medicine and Health Sciences
                Oncology
                Basic Cancer Research
                Metastasis
                Biology and life sciences
                Genetics
                Gene expression
                Gene regulation
                Small interfering RNA
                Biology and life sciences
                Biochemistry
                Nucleic acids
                RNA
                Non-coding RNA
                Small interfering RNA
                Research and analysis methods
                Specimen preparation and treatment
                Staining
                Nuclear staining
                DAPI staining
                Custom metadata
                All relevant data is included in the paper, but may contain potentially sensitive information which cannot be made publicly available. Clinical data is maintained in a secure database in the Hayes laboratory. To request access to clinical data, permission must be granted by the University of Michigan Medical School Institutional Review Board (IRBMED) at 2800 Plymouth Road, Building 520, Room 3214, Ann Arbor, MI 48109-2800 (Telephone: 734-763-4768; Fax: 734-763-1234; e-mail: irbmed@ 123456umich.edu ).

                Uncategorized
                Uncategorized

                Comments

                Comment on this article