When immune or tumor cells are stimulated by both internal and external factors, HMGB1 can be secreted into the extracellular space, where it binds to various receptors on the cell membrane, such as the advanced glycation end product (RAGE) receptor, Toll-like receptors, CXCL4, TIM-3, and others. The gene discussed is HAVCR2; the disease is neoplasm.