TIM-3/HMGB1 pathway: which can attenuate the innate immune activation by blocking dendritic cells from recognizing the nucleic acids originating from tumors, and which in turn suppresses tumor immune surveillance (15, 16); TIM-3/PtdSer pathway: helps to clear apoptotic cells and inhibit immune hyperactivation under normal conditions; in tumor or chronic inflammatory environments, it may be exploited by tumor cells to evade immunity (17). This evidence concerns the gene HMGB1 and neoplasm.