The kynurenine pathway of cancer invasion and immune escape.

FromCancer: Why tumours eat tryptophan

• George C. Prendergast

Nature

 

478,

 

192–194

 

(13 October 2011)

 

doi:10.1038/478192a

Indoleamine 2,3-dioxygenase (IDO) enzymes generate the compound kynurenine in tumour and immune cells. Opitz et al.¹ find that another enzyme, tryptophan dioxygenase (TDO), also generates kynurenine in tumour cells, and that kynurenine acts as a signal for the aryl hydrocarbon receptor (AHR). a, Kynurenine generated by a tumour cell may activate AHRs on the same cell, causing the receptors to translocate to the cell's nucleus (not shown), where they regulate the expression of target genes that help tumour cells migrate. b, Binding of kynurenine to AHRs on certain immune cells (effector T cells; Teff) that recognize tumour cells suppresses the activity of the Teff cells, helping tumours to evade immune responses. c, The binding of kynurenine to other tumour-targeting immune cells — dendritic cells and regulatory B (Breg) cells — increases immune tolerance. d, Immune tolerance can spread from the tumour's microenvironment when dendritic cells and Breg cells move to lymph nodes and stimulate the generation of tumour-promoting regulatory T cells, thereby facilitating metastasis