Chapter 23: Role of kynurenine pathway in hematological malignancies

Abstract

Similarly to solid tumors, hematological malignancies create an immunosuppressive microenvironment, where both innate and adaptive immune responses are profoundly deregulated. Some recent reports have shed new light on the mechanisms underlying the induction of immunological tolerance by leukemic cells. Among these, tryptophan catabolism toward kynurenines by indoleamine 2,3- dioxygenase 1 (IDO1) has been recently described as a potent immunosuppressive pathway in several hematological tumors. The fi rst evidence of a role of kynurenine pathway in regulating immune escape was described in acute myeloid leukemia (AML). Such preliminary fi nding has been recently extended to pediatric leukemias and Hodgkin and non-Hodgkin lymphomas. The tolerogenic activity of IDO1 has been reported both as a consequence of IDO1 expression by leukemia/lymphoma cells and by an increased IDO1 activity in the tumor microenvironment. The immunosuppressive role of IDO has been recently investigated for the induction of graft tolerance, including allogeneic stem cell transplantation (SCT), which represents a fundamental therapeutic strategy in the management of most hematological malignancies. In this context, some recent reports have indicated IDO1 as a critical regulator of graft-versus-host disease (GVHD). Aim of this chapter is to summarize the most signifi cant and recent advances in the fi eld.