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). This evidence concerns the gene NT5E and central nervous system cancer.