Macrophage targeting in meningioma: tumor-associated immune niche determines differential sensitivity to CSF1R blockade ex vivo

Meningiomas are highly infiltrated by immunosuppressive tumor-associated macrophages (TAMs), yet how CSF1R inhibition reshapes TAM function and anti-tumoral T-cell activity in human disease remains unclear. Here, we show that CSF1R blockade of TAMs induces heterogeneous ex vivo responses across patient-derived meningioma samples, which are differentiated into responder, intermediate, and non-responder groups using an experimental treatment score. Responder-TAMs undergo robust phenotypic, transcriptional, and functional repolarization, driving potent anti-tumoral T-cell activation, whereas TAMs of non-responders remain insensitive. Single-cell and independent spatial transcriptomics reveal distinct immune niches linked to ex vivo responsiveness: non-responder samples harbor more immunosuppressive TAM populations, while tumors of responders are enriched for effector T-cells, dendritic cells, and stress-associated macrophages, accompanied by distinct translational and spatial ecosystems. These findings highlight the tumor immune niche as a key determinant of ex vivo anti-CSF1R sensitivity and provide a potential framework for patient stratification in future immunotherapy-based clinical trials for human meningioma.