Pro-coagulant platelets promote immune evasion

 

Introduction In addition to tumor cells, cells in the tumor environment including platelets synthesize immune checkpoint (IC) molecules. The role of these cellular blood components for the regulation of intratumoral immune cell responses remain unclear.

Materialand methods Different mouse models of cancer were utilized together with in vitro assays to characterize the role of platelets for the regulation of intratumoral immune cell responses. As a translational perspective, analyses in human blood and in RNA sequencing data of human tumors were performed.

Results Here, we report that pro-coagulant platelets bear large amounts of such immunomodulatory factors and that the presence of these cellular blood components in malignant tumors relates to pro-tumorigenic immune cell activity and impaired survival. Mechanistically, tumor-released nucleic acids attract platelets into the aberrant tumor microvasculature where they undergo pro-coagulant activation, thus delivering specific stimulatory and inhibitory IC molecules. This concomitantly promotes pro-tumorigenic myeloid leukocyte responses and compromises anti-tumorigenic lymphocyte activity, ultimately supporting tumor growth. Interference with platelet-leukocyte interactions prevented immune cell misguidance and suppressed tumor progression.

Conclusion / Discussion Our data uncover a self-sustaining mechanism of solid malignancies in utilizing platelets to misdirect immune cell responses. Targeting this irregular multicellular interplay might represent a novel immunotherapeutic strategy in head and neck squamous cell carcinoma without side effects of systemic IC inhibition.

Funding information This study was supported by the "Deutschen Forschungsgemeinschaft" (DFG), Collaborative Research Centre (SFB) 914, Projekt B03

Publication History

Article published online:
19 April 2024

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