Three additional ligands bind to TIM-3 and regulate antitumor immunity: Galectin-9 interacts with TIM-3 via its glycan chain to modulate TH1 cell immunity through apoptosis; TIM-3 facilitates the clearance of apoptotic bodies in the tumor microenvironment (TME) by interacting with PtdSer; and the HMGB1-TIM-3 interaction disrupts the innate immune response to nucleic acids mediated by Toll-like and cytoplasmic receptors, thereby reducing the effectiveness of DNA vaccines and cytotoxic chemotherapy (Andrews et al., 2019). Here, HAVCR2 is linked to neoplasm.