Programmed Death-Ligand 1 and Programmed Death-Ligand 2 mRNAs Measured Using Closed-System Quantitative Real-Time...

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Immune checkpoint inhibitors (ICIs) are standard lung cancer treatment, but response rates are limited.
• Current biomarkers like PD-L1 protein are insufficient for predicting ICI response, especially in the adjuvant setting.
• There is a need for improved methods to identify patients who will not respond to ICIs.

Purpose of the Study:

• To investigate programmed death-ligand 1 (PD-L1) mRNA expression as a predictive biomarker for ICI nonresponse in lung cancer.
• To evaluate the association between PD-L1, PD-L2, CD8A, and IRF1 mRNA levels and response to ICI therapy.
• To determine the utility of PD-L1 mRNA assessment for patient selection in advanced and adjuvant settings.

Main Methods:

• A quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) assay was used.
• The study analyzed mRNA expression of CD274 (PD-L1), PDCD1LG2 (PD-L2), CD8A, and IRF1.
• Tissues from 122 advanced non-small cell lung cancer (NSCLC) patients were analyzed retrospectively before ICI therapy.

Main Results:

• High PD-L1 and PD-L2 mRNA expression correlated with improved 24-month benefit and overall survival (p=0.047-0.049).
• PD-L1 and PD-L2 mRNA levels were elevated in patients with KRAS mutations.
• Low PD-L1 mRNA expression demonstrated a high negative predictive value (0.92) for lack of long-term benefit.

Conclusions:

• PD-L1 mRNA assessment could identify lung cancer patients unlikely to benefit from adjuvant ICI therapy.
• This mRNA-based approach may serve as an objective method for selecting patients for ICI treatment.
• Further validation in low-stage patients is warranted to confirm its clinical utility.