The kynurenine pathway presents multi-faceted metabolic vulnerabilities in cancer

Abstract

The kynurenine pathway (KP) and associated catabolites play key roles in promoting tumor progression and modulating the host anti-tumor immune response. To date, considerable focus has been on the role of indoleamine 2,3-dioxygenase 1 (IDO1) and its catabolite, kynurenine (Kyn). However, increasing evidence has demonstrated that downstream KP enzymes and their associated metabolite products can also elicit tumor-microenvironment immune suppression. These advancements in our understanding of the tumor promotive role of the KP have led to the conception of novel therapeutic strategies to target the KP pathway for anti-cancer effects and reversal of immune escape. This review aims to 1) highlight the known biological functions of key enzymes in the KP, and 2) provide a comprehensive overview of existing and emerging therapies aimed at targeting discrete enzymes in the KP for anti-cancer treatment.

Prognostic relevance of high expression of kynurenine pathway markers in glioblastoma

“…The dysregulation of the kynurenine pathway is thought to be responsible for a poor prognosis due to its effect on the tumour immune environment 5 , 6 . The upregulation of KP is linked to immune evasion of tumour cells by controlling the differentiation and effector functions of T-cells, lymphocytes, and macrophages 10 – 14 , 30 .…”

“…Recently, the kynurenine pathway (KP) has entered the stage as a key regulator of the tumour immune microenvironment in GBM 5 , 6 . The KP represents a metabolic pathway (Fig.…”