MEG3 overexpression promotes M1 macrophage polarization, increases Th1 cytokines, and reduces CSF-1 and PD-1/PD-Ls, inhibiting HCC growth, invasion, and migration. MEG3 knockdown (KD) induces M2 polarization, elevates Th2 cytokines, CSF-1, and PD-1/PD-Ls, and promotes tumor growth. In vivo, MEG3 OE inhibits tumor growth and PD-1/PD-Ls while enhancing Th1 immunity, whereas MEG3 KD has the opposite effect. The gene discussed is CSF1; the disease is hepatocellular carcinoma.