HAVCR2 and cancer: Although some in vitro studies indicate TIM3 as a co-stimulatory receptor in TCR signaling [58,59], however, TIM3 is widely accepted as a co-inhibitory receptor due to the link between loss-of-function mutations of TIM3 gene and its polymorphisms with autoinflammatory conditions [60], as well as some promising clinical trials targeting TIM3 in cancer patients [61].