Targeting the IDO1/TDO2–KYN–AhR Pathway for Cancer Immunotherapy – Challenges and Opportunities

IDO1 and TDO2 catalyze the commitment and rate-limiting step of the KYN metabolic pathway that produces the endogenous AhR agonist KYN. Activation of AhR by KYN contributes to the immunosuppressive tumor microenvironment and supports cancer immune escape. Three differential therapeutic modalities, each intercepting a unique node of the IDO1/TDO2–KYN–AhR enzymatic/signaling cascade, have been pursued for the development of novel cancer...