Integrated assessment of IDO1 activity and PD L1 expression reveals immunometabolic alterations in non small cell lung cancer

IDO1 contributes to tumor-associated immunosuppression by regulating tryptophan catabolism. This study investigated the immunometabolic tryptophan-kynurenine axis in NSCLC by evaluating circulating tryptophan metabolites, the IDO1 rs10089084 genetic variation, IDO1/PD-L1 expression in tumor tissues of NSCLC patients, and soluble sPD-1 in relation to clinicopathological features. Seventy NSCLC patients and 72 healthy controls were included in the study. Plasma TRP, KYN, and KYNA levels were analyzed by high-performance liquid chromatography, IDO1 rs10089084 gene variants by PCR–RFLP, IDO1/PD-L1 expression levels in tumor and adjacent non-tumor tissues by quantitative PCR, and sPD-1 levels by ELISA. Lower TRP levels, higher KYN levels, and increased KYN/TRP ratios were detected in individuals with the IDO1 CC genotype. Correlation analyses supported a possible association between systemic tryptophan-kynurenine metabolism and intratumoral IDO1/PD-L1-related immune-metabolic activity. ROC results demonstrated that decreased TRP and increased KYN/TRP values can differentiate NSCLC patients from healthy controls. Locally advanced disease was associated with lower TRP levels and increased KYN/TRP ratios compared to early-stage disease. Our findings suggest that integrated assessment of TRP-KYN pathway metabolites with IDO1 genetic variation and IDO1/PD-L1 expression may aid in characterizing immunometabolic alterations in NSCLC and support the development of biomarker-based approaches for disease stratification and progression assessment.