Indoleamine 2,3-dioxygenase: From tolerance during pregnancy to cancer

During pregnancy, the foetus expresses paternal antigens that do not provoke rejection by the mother, as would any other semi-allogeneic graft. In this tolerance, several systems are implicated, including the enzyme indoleamine 2,3-dioxygenase (IDO), which catalyses the first step in the tryptophan degradation pathway. IDO-mediated tryptophan depletion provokes an inhibition of T-cell responses, which cannot get through a checkpoint in the G1 phase of cell cycle. Several tumours can express IDO ectopically, enabling them to evade the immune attack. Dendritic cells can also express IDO and thus, induce a tolerogenic response. IDO enzyme could be a new immunotherapeutic target because its inhibitors can slow tumour growth and, if administered together with chemotherapeutic agents, they produce tumour regression. The knowledge of tolerogenic capacity of tumours helps not only in the understanding of cancer growth but also in developing new therapeutic approaches.