The potential of targeting indoleamine 2,3-dioxygenase for cancer treatment

Introduction: Degradation of the essential amino acid tryptophan via indoleamine 2,3-dioxygenase (IDO1) represents an important antiproliferative strategy of the cellular immune response. Tryptophan shortage and accumulation of kynurenine downstream products also affect T-cell responses, providing a negative feedback control of immune activation. IDO1 activity can promote a regulatory phenotype in both T cells and dendritic cells. These phenomena can support tumor immune escape. Areas covered: IDO1 activity reflects the course of several malignancies, and determination of kynurenine to tryptophan ratio in serum/plasma can be used to assess immune activation. Moreover, the accelerated breakdown of tryptophan has been correlated with the development of cancer-associated disturbances such as anemia, weight loss and depression. Tumoral IDO1 expression was correlated with a poor prognosis in several types of tumors, which makes it to an interesting target for immunotherapy. In addition, according to recent data, a role of trytptophan 2,3-dioxygenase (TDO) in tumorigenesis cannot be excluded. Expert opinion: Tryptophan metabolism is critical for cell proliferation, inflammation and immunoregulation. Accelerated tryptophan breakdown favors tumor immune escape. Accordingly, targeting IDO1 by immunotherapy may represent a favorable approach; however, blocking crucial immunoregulatory pathways could also introduce the risk of immune system overactivation, finally leading to unresponsiveness.