HAVCR2 and colorectal carcinoma: In CRC, Xu et al. showed that the level of tumor-infiltrating CD8 T cells producing IFN-γ was greatly reduced when they express both PD-1 and TIM3 as compared to PD-1– TIM-3– or PD-1+ TIM-3– CD8 T cells, suggesting a more dysfunctional state of PD-1+ TIM-3+ CD8 T cells than PD-1+ TIM-3– CD8 T cells (137).