Related Experiment Video
Updated: Sep 12, 2025
Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids
Published on: November 22, 2021
Investigating the correlation between IDO1/PD-L1 expression or co-expression and EGFR/KRAS gene mutations in advanced
Zhidong Yin1, Bohao Sun1, Lu Cheng1
1Department of Pathology, Second Affiliated Hospital, Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou, 310009, Zhejiang Province, China.
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.
Insights
This study found indoleamine 2,3-dioxygenase 1 (IDO1) and programmed death-ligand 1 (PD-L1) are often co-expressed in non-small cell lung cancer (NSCLC). Targeting these pathways may improve outcomes for advanced NSCLC patients.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Lung cancer, particularly non-small cell lung cancer (NSCLC), is often diagnosed at advanced stages, leading to poor survival rates.
- Despite advances in immunotherapy and targeted therapies, drug resistance remains a significant challenge in NSCLC treatment.
- Indoleamine 2,3-dioxygenase 1 (IDO1) and programmed death-ligand 1 (PD-L1) are key immune checkpoint molecules implicated in cancer progression and immune evasion.
Purpose of the Study:
- To investigate the co-expression patterns of IDO1 and PD-L1 in NSCLC patients.
- To evaluate the relationship between IDO1/PD-L1 expression and treatment response across different therapies (targeted therapy, chemotherapy, immunotherapy).
- To explore the correlation of IDO1/PD-L1 expression with EGFR mutation status and its impact on overall survival (OS).
Main Methods:
- Analysis of IDO1 and PD-L1 expression in tumor cells from NSCLC patients.
- Correlation of expression levels with patient treatment history (targeted therapy, chemotherapy, immunotherapy).
- Assessment of IDO1/PD-L1 expression in relation to EGFR mutation status and its impact on overall survival.
Main Results:
- Significant co-expression of IDO1 and PD-L1 was observed in NSCLC.
- Elevated IDO1 expression was noted in tumor cells following various treatments, including targeted therapy, chemotherapy, and immunotherapy.
- EGFR wild-type patients predominantly showed IDO1/PD-L1 co-expression or single positivity, while EGFR-mutant cases were more frequently co-negative or single-negative.
- PD-L1 single-positive patients demonstrated significantly or marginally prolonged OS compared to other expression groups, particularly in EGFR wild-type subgroups.
Conclusions:
- IDO1 and PD-L1 co-expression is a relevant finding in NSCLC, influenced by treatment and EGFR mutation status.
- PD-L1 positivity, especially in EGFR wild-type NSCLC, is associated with improved survival outcomes.
- Combined targeting of IDO1 with PD-L1, EGFR, or KRAS pathways presents a potential therapeutic strategy for advanced NSCLC.
