Studies showed that TIM-3 and PD-1 co-expression on CD8+ T cells exhibits more exhausted phenotypes, as defined by failure in cytokine secretion including interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin-2 (IL-2) in CRC patients [32]. This evidence concerns the gene HAVCR2 and colorectal carcinoma.