HMGB1 and hepatocellular carcinoma: Similarly, in hepatocellular carcinoma (HCC), tumor-derived HMGB1 engages TLR2 on macrophages, triggering a NOX2/ROS-dependent autophagic response that drives M2 macrophage polarization, thereby creating an immunosuppressive and pro-tumorigenic niche [105] (Figure 2).