HMGB1 (High-Mobility Group Box 1)

HMGB1 (High-Mobility Group Box 1) is a nuclear DNA-binding protein that can also act, once released into the extracellular space, as an alarmin — an endogenous damage or stress signal that activates innate and adaptive immune responses via receptors such as RAGE. HMGB1 release can occur through passive mechanisms during cell death or through active, regulated secretory pathways, and its downstream signaling has been linked to activation of antitumor CD8+ T-cell immunity as well as broader immunoinflammatory and interferon responses.