SPP1 and central nervous system cancer: Tissue biomarkers that index SPP1+ TAM programs and perivascular SPP1–CD44 signaling associate with mesenchymal traits and poor outcome in glioma and can be captured by RNA panels or multiplexed protein assays (40, 68, 69); spatial adjacency metrics such as CD39+ myeloid–CD73+ tumor proximity and enrichment of HMOX1+ IL-10–secreting myeloid neighborhoods provide orthogonal evidence of immunosuppressive niches and should be prospectively standardized as pharmacodynamic endpoints (39, 70, 71).