TNF and infection: TNF was first isolated as a crucial factor responsible for endotoxin-induced hemorrhagic necrosis of tumors.320 The cloning of the TNF gene in the 1980s expanded the understanding of its role, revealing its identity as cachectin, a key player in the physiological responses to infection, including acute shock and chronic cachexia.321 Subsequent research highlighted the complex role of TNF in cancer, initially seen as a promising anti-cancer agent due to its ability to induce tumor necrosis.322 However, its potential as a therapeutic has been limited by a narrow therapeutic window.