Splenic granulopoiesis and S100A9 drive resistance to checkpoint inhibitors conferred by liver metastases
Rebecca J. Lee, Steven Hooper, Laura J. Pallett, Mariana O. Diniz, Tate Mckinnon-Snell, Zoe Ramsden, Nicolas Rabas, Stefan Boeing, Oliver John Kennedy, Charlotte Buttercase, Gloryanne Aidoo-Micah, Gareth J. Price, Sarah C. Macfarlane, Sasha Bailey, Jessica E. Davies, , Erik A. Sahai
This study shows liver metastases reduce checkpoint inhibitor efficacy by increasing splenic granulopoiesis and S100A9hi neutrophils, which suppress T-cell responses, and demonstrates that targeting S100A9 restores efficacy.
bioRxiv · Sep 30, 2025 · PreprintImmunology