Indeed, several tumorigenic and angiogenic factors, such as VEGF and IL-10, released by the tumor in situ induce TIM-3 expression on TIDC surface, resulting in the suppression of innate immune responses to nucleic acids by binding to the damage-associated molecular pattern molecule, HMGB1 (Chiba et al., 2012; Mattei and Schiavoni, 2013). This evidence concerns the gene HAVCR2 and neoplasm.