It can facilitate oxygen release from hemoglobin and increase tissue oxygen levels to consistently and reproducibly increase tumor oxygenation when used in combination with radiation therapy.48, 49, 50 The expression of JAK2 and STAT3, which can promote M2-type macrophage polarization, is significantly decreased after stimulation with hesperidin derivatives-12 (HDND-12) in M1-like TAMs.51 The gene discussed is STAT3; the disease is neoplasm.