These TAMs then secrete interleukin-27 (IL-27), which induces CD8+ T cells to upregulate the immune checkpoint molecule TIM-3 and decrease the expression of TNF-α and IFN-γ, leading to CD8+ T cell exhaustion and facilitating immune evasion.645 Furthermore, liver cancer cells activate the Smad signaling pathway through TGF-β in the microenvironment, which in turn activates the expression of the downstream molecule SOX18. This evidence concerns the gene CD8A and liver cancer.