Also, CAFs inextricably create crosstalk with diverse immune cell types in the TME, causing the inter alia inhibition of NK cell and T-cell activity against HCC through various secreted mediators, e.g., PGE2, indoleamine 2,3-dioxygenase (IDO), or IL-6, and thereby lead to immunosuppression that favors HCC development and invasion [90]. This evidence concerns the gene IDO1 and hepatocellular carcinoma.