Abstract / Description
BackgroundThe kynurenine pathway is a key immunosuppressive mechanism implicated in resistance to immune checkpoint inhibitors (ICIs). This study investigated expression of tryptophan-metabolising enzymes (IDO1, TDO2, IL4I1) and their relationship with the immune microenvironment across molecular subtypes of endometrial cancer (EC).MethodsA cohort of 570 ECs was classified as mismatch repair-deficient (MMRd), p53-mutant (p53mut), or no specific molecular profile (NSMP). Expression of IDO1, TDO2, IL4I1, PD-L1, kynurenine, and immune markers (CD8, FOXP3, CD68, CD163) was assessed by immunohistochemistry and quantified in tumour and stromal compartments using QuPath. Associations with disease-specific survival (DSS) were analysed using correlation testing, Kaplan-Meier, and Cox regression.ResultsIDO1, TDO2, and IL4I1 correlated strongly with immune infiltrate density. High IDO1 tumour expression was linked to improved DSS in NSMP and p53mut tumours (p