Tumor-derived SPP1 signaling recruits and polarizes APOE+ macrophages to the peri-tumoral regions and tumor borders, where they secrete TGF-β, upregulated CEBPD, and triggered PD-L1 signaling, forming a physical and functional barrier between CD8+ T cells and malignant cells, thereby effectively dampening immune responses. The gene discussed is TGFB1; the disease is neoplasm.