Abstract
Lung cancer was frequently diagnosed at advanced stages (III/IV) and exhibited poor 5-year survival due to limited treatment efficacy. While immunotherapy and targeted therapies had advanced care, drug resistance persisted as a critical challenge. Our study revealed significant IDO1/PD-L1 co-expression in NSCLC. Tumor cells from patients treated with targeted therapy, chemotherapy, or immunotherapy (mono- or combination therapy) demonstrated elevated IDO1 expression. EGFR wild-type patients predominantly showed individual or co-positive IDO1/PD-L1 expression, whereas EGFR-mutant cases typically exhibited co-negative or single-negative profiles. Notably, PD-L1 single-positive patients achieved significantly or marginally prolonged OS compared to IDO1 single-positive, co-positive, or co-negative cohorts, with this survival benefit being most pronounced in EGFR wild-type subgroups. These results indicated that combined targeting of IDO1 with PD-L1/EGFR/KRAS pathways might represent a viable therapeutic approach for advanced NSCLC.