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

Schlueter, Julian; Cunningham, Sarah; Zimmermann, Robert; Achenbach, Susanne; Kramer, Rafaela; Erdmann, Michael; Beckmann, Malte; Heinzerling, Lucie und Hackstein, Holger (2022): Characterization of the impact of immune checkpoint inhibitors on platelet activation and aggregation. In: Immunobiology, Bd. 228, Nr. 1, 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 po-tential direct and indirect effect of PD-1, PD-L1 and CTLA-4-targeting ICIs on platelet functionality in multi-faceted 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0171-2985
• Sprache: Englisch