Extended Data Fig. 10: Schematic illustration of macrophage specialization and T cell interactions in human and mouse GBM models following various treatment regimens.

Recurrent GBM tumors are associated with angiogenesis, loss of microglial cells, and progressively increased infiltration of monocyte-derived TAMs. SIGLEC9+ TAMs persist after neoadjuvant anti-PD-1 therapy, especially in non-responders. Targeting Siglec-E (murine homolog of Siglec-9) in mouse GBM models on macrophages priorly activates T cells via secretion of chemokines, interaction with co-stimulation factors and upregulation of IFN-γ-related pathways thereby enhancing the anti-PD-1/PD-L1 therapy efficacy. Thus, Siglec-9/Siglec-E represents an immune checkpoint on macrophages and is a potential target for cancer immunotherapy.