An early in vitro study illustrated that CAFs deactivate natural killer (NK) cells and impair their cytotoxicity against HCC cells by secreting prostaglandin E2 (PGE2) and indoleamine 2,3-dioxygenase (IDO), and interestingly, the release of these factors depends on the presence of NK cells, implying plausible crosstalk between CAFs and NK cells in the HCC TME.56 This evidence concerns the gene IDO1 and hepatocellular carcinoma.