IDO⁺ DCs and signalling pathways

Dendritic cells (DCs) have traditionally been viewed as constituting an 'information management' system that functions solely to integrate a diverse array of incoming signals, in order to induce immune reactivity. In recent years, however, there has been a shift towards viewing these cells as key regulators in the orchestration of immunological tolerance, with increasing recognition that they are capable of suppressing T-cell responses depending on signalling processes and localised biochemical conditions. Indoleamine 2,3-dioxygenase (IDO) competent (IDO⁺) DCs are a subset of human DCs which are programmed to a tolerogenic state and play a vital role in establishing and maintaining a tumour-suppressing milieu. The expression of IDO in these DCs represents a key mechanism responsible for inducing the tolerogenic state. However, the mechanisms by which IDO becomes dysregulated in this subset of DCs have not yet been described. In this review, the function of IDO⁺ DCs within the cancer-tolerogenic milieu, as well as the signals responsible for expression of IDO in this subset, will be discussed.