On the other hand, HMGB1 produced by the tumor-specific macrophages can regulate the microenvironment through IL-6/STAT3/(programmed death-ligand 1) PD-L1 pathway and IL-6/NF-κB/(matrix metalloproteinase 9) MMP-9 pathway leading to further immunosuppression and aggressive phenotypes of OSCC cells. The gene discussed is MMP9; the disease is neoplasm.