The HMGB1 as a damage-associated molecular pattern (DAMP) that binds to DNA released from dying cells boosts nucleic acid sensing by toll-like receptors (TLRs), but during chronic infection and cancers, due to HMGB1 binding to TIM-3 expressed on APCs, it seems that this interaction suppresses innate immune responses to the nucleic acid (Figure 1A) (13, 21). The gene discussed is HAVCR2; the disease is cancer.