Metformin decreases infiltration of FOXP3+ T regulatory cells in intratumor regions, increases CD8+ cytotoxic T cell infiltration in the peritumoral leading edge stroma, and increases the CD8/FOXP3 ratio both in the tumor and leading-edge stroma of primary HNSCC tumors [137]. The gene discussed is FOXP3; the disease is head and neck squamous cell carcinoma.