Tumor-derived SPP1 promotes the polarization of macrophages into APOE+ M2-like macrophages, upregulates CEBPD, inhibits the release of chemokines, enhances the activation of the PD-L1 pathway, and modulates immune suppressive signals such as TGF-β and IL-10, thereby shaping an immunosuppressive microenvironment. The gene discussed is CEBPD; the disease is neoplasm.