TIM-3 interacts with multiple ligands, such as Galectin-9 (Yang et al., 2021), CEACAM1(Huang et al., 2015), phosphatidylserine (PtdSer) (DeKruyff et al., 2010), and HMGB1 (Tang and Lotze, 2012), promoting tumor immune tolerance and CD8+ T-cell exhaustion, thus facilitating tumor progression (Dixon et al., 2021). This evidence concerns the gene HMGB1 and neoplasm.