Less is known about the function of TDO in cancer. Under physiologic conditions TDO is almost exclusively expressed at high amounts in the liver and – in lower levels – in the brain. Recently, it was described that tumors of different origin express TDO, especially melanoma, bladder cancer, hepatocellular carcinoma and glioblastoma. It still remains to be established, however, to which extent TDO and/or IDO contribute to cancer-associated immune suppression: in a series of human tumor cell lines of various histological types, tumors expressed only TDO, only IDO and both enzymes. Moreover, in a preclinical model, TDO expression by tumors prevented their rejection by mice immunized against the respective TDO-negative tumor.
Hjorts? MD, Larsen SK, Kongsted P, et al. Tryptophan 2,3-dioxygenase (TDO)-reactive T cells differ in their functional characteristics in health and cancer. Oncoimmunology. 2015;4(1):e968480.