Characterization of the impact of immune checkpoint inhibitors on platelet activation and aggregation

Schlüter J, Cunningham S, Zimmermann R, Achenbach S, Kramer R, Erdmann M, Beckmann M, Heinzerling L, Hackstein H (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Immunobiology Elsevier

Book Volume: 228

Article Number: 152311

Journal Issue: 1

DOI: 10.1016/j.imbio.2022.152311

Abstract

Immune checkpoint inhibitors (ICIs) are effective oncological drugs which block cellular check-point receptors typically targeted by tumor immune evasion strategies. Despite their benefits, clinicians have reported treatment-associated thromboembolism during ICI therapy in recent years. Though several theories on this ICI-associated pathogenesis exist, the direct effects of ICIs on platelets remains unknown. We therefore investigated the potential direct and indirect effect of PD-1, PD-L1 and CTLA-4-targeting ICIs on platelet functionality in multifaceted in vitro experiments. Interestingly, we could not observe a clear effect of ICI on platelet aggregation and primary hemostasis in whole blood and platelet concentrate-based assays. Furthermore, the presence of ICIs in toll-like receptor stimulation had no significant impact on platelet surface marker expression. In a second approach, we investigated the indirect immunological impact of ICIs on platelet activation by exposing platelets to supernatants from ICI- and Staphylococcal enterotoxin B-exposed PBMCs. Whereas ICIs affected IL-2 levels in supernatants, we could not detect clear differences in the secretion of pro-thrombogenic factors and platelet responses. The obtained data suggest that the direct influence of ICIs on platelet activation or the influence of altered T cell function on platelet activation cannot be considered a major factor in the development of thrombotic events.

Authors with CRIS profile

Sarah Cunningham Department of Transfusion Medicine and Haemostaseology Robert Zimmermann Department of Transfusion Medicine and Haemostaseology Susanne Achenbach Department of Transfusion Medicine and Haemostaseology Rafaela Kramer Department of Dermatology Michael Erdmann Department of Dermatology Matthias Beckmann Lehrstuhl für Geburtshilfe und Frauenheilkunde Lucie Heinzerling Department of Dermatology Holger Hackstein Professur für Transfusionsmedizin und Cell-Engineering

How to cite

APA:

Schlüter, J., Cunningham, S., Zimmermann, R., Achenbach, S., Kramer, R., Erdmann, M.,... Hackstein, H. (2023). Characterization of the impact of immune checkpoint inhibitors on platelet activation and aggregation. Immunobiology, 228(1). https://doi.org/10.1016/j.imbio.2022.152311

MLA:

Schlüter, Julian, et al. "Characterization of the impact of immune checkpoint inhibitors on platelet activation and aggregation." Immunobiology 228.1 (2023).

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