These data support a circuit topology in which perivascular SPP1–CD44 and angiogenic signals consolidate mesenchymal programs and vascular remodeling; perinecrotic hubs concentrate IL-10–dominated myeloid signaling and adenosine metabolism; and border zones variably permit lymphoid ingress depending on TAM continuity at tumor–stroma interfaces (55, 66, 67). Here, SPP1 is linked to neoplasm.