IP6K1-driven tumour polyphosphate may contribute to immune checkpoint inhibitor-associated thrombosis

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Published: 17 Dec 2025
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Dr Keith McCrae - Cleveland Clinic, Cleveland, USA

Dr Keith McCrae speaks to ecancer about research on immune checkpoint inhibitor–associated thrombosis presented at ASH 2025.

The study shows that immune checkpoint inhibitor treatment increases contact system activation and thrombotic risk in both murine models and cancer patients.

Dr McCrae explains that ICI therapy upregulates tumour expression of inositol hexakisphosphate kinase 1 (IP6K1), driving polyphosphate production in a T cell–dependent manner.

He reports that tumour-derived polyphosphate may activate factor XII and amplify thromboinflammation, highlighting the IP6K1–polyphosphate axis as a potential therapeutic target to reduce thrombosis during cancer immunotherapy.