Figure 1.

The Try-IDO1/TDO-KYN pathway and immune escape. IDO1 is constitutively expressed in fibroblast, tumor cells, and DCs, and can be upregulated by IL-10 and IFN-γ, whereas TDO is only expressed in hepatocytes. When IDO1 and TDO are activated, they promote Try degradation and KYN accumulation. Try depletion can activate GCN2 and inhibit the mTORC1 signaling. The KYN can bind to AhR in NK cells, Tregs, and DCs. Therefore, the Try-IDO1/TDO-KYN pathway cooperatively modulates immune cells (e.g., DCs, macrophage, Treg, and T cells) to regulate anti-inflammatory cytokine production, leading to enhanced immunosuppression in the tumor microenvironment.