Phytochemical Modulation of the Kynurenine Pathway (KYNP) and Its Emerging Mechanistic Insights into Cancer...

Dysregulation of the kynurenine pathway (KYNP) is increasingly recognized as a hallmark of cancer-associated metabolic reprogramming, contributing to immune evasion, oxidative stress, and tumor progression through the activity of enzymes such as indoleamine 2,3-dioxygenase 1 (IDO1), indoleamine 2,3-dioxygenase 2 (IDO2), and tryptophan 2,3-dioxygenase (TDO2). This systematic review aimed to evaluate the current evidence on the ability of phytochemicals to modulate the KYNP and their potential implications for cancer prevention and therapy. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and included English-language articles and book chapters published between 2016 and 2026 that were retrieved from the Scopus and PubMed databases. A keyword co-occurrence network was generated using VOSviewer (v1.6.20) based on the complete Scopus and PubMed exports of the included studies to identify major research themes. The available evidence indicates that phytochemicals restore anticancer immunity by targeting multiple components of the KYNP, including inhibition of IDO1-mediated kynurenine production and suppression of downstream aryl hydrocarbon receptor signalling, thereby enhancing cytotoxic T-cell responses, reducing immunosuppressive cell populations, and improving antitumor immune activity. Collectively, these findings support the KYNP as a promising immunometabolic target and highlight phytochemicals as potential complementary agents for cancer immunotherapy while emphasizing the need for further investigation of the biological and immunological roles of IDO2.