HAVCR2 and cancer: Therefore, considering that TIM-3 can reduce the antigen-specific T cell responses and down-regulate the anti-tumor immunity in vivo by inhibiting the Th1 responses [16], we speculated that TIM-3 polymorphisms (−1516G/T, −1516G/T, and +4259T/G) conferred individual risk for cancer by increasing TIM-3 expression or enhancing TIM-3 activity.