IDO Immune Pathway

The IDO pathway prevents the body’s immune system from over-responding to threats, and therefore causing unnecessary damage to its healthy cells.

IDO exhibits its immune-dampening effect by suppressing the response of macrophages and effector T cells. The exact mechanism of this immunosuppression is unclear, but it likely involves tryptophan starvation of sensitive T-cells and/or the build-up of toxic metabolites (kynurenines) from tryptophan metabolism, leading to cell cycle arrest and death of effector T cells within the surrounding environment. IDO expression also directly activates the regulatory T cells that actively suppress the immune response, which amplifies the suppressive effect.

Immune evasion is one of the identifying hallmarks of cancer, and researchers are trying to identify the complex mechanisms that enable cancer cells to evade the host’s immune system.

Cancer cells use the IDO pathway to suppress the host’s immune response in order to facilitate survival, growth, invasion, and metastasis of malignant cells. The IDO pathway is active in many tumors, providing a direct defense against T cell attack, allowing the tumor cells to evade destruction by the immune system.

Targeting the IDO pathway has been recognized as a key strategy in the development of cancer therapies, with various IDO inhibitors in pre-clinical and clinical stages.