PhD Defense: Biomarkers for clinical benefit to immune checkpoint blockade treatment in NSCLC

PD-1/PD-L1 blocking agents have greatly improved the treatment of advanced stage non-small cell lung cancer (NSCLC). These immune checkpoint inhibitors can induce long-lasting responses. However, 60% to 70% of patients experience disease progression within six months of treatment. This leads to unnecessary side effects, costs, and delays in trying alternative treatments. Therefore, finding predictive biomarkers to identify which patients won’t benefit from PD-(L)1 blockade therapy is crucial. 

In this thesis, the presence of a distinct population of tumor-reactive T cells, known as PD-1T TILs, was established as a novel biomarker for both long-term benefit and lack of benefit to PD-1 blockade in NSCLC. The researchers developed an mRNA test to detect these TILs, making it easier to use in routine diagnostics. This thesis also explored less invasive methods for assessing treatment effectiveness. A blood-based protein test was developed to predict patient outcomes without the need for tissue samples. Additionally, the researchers found that cell-free DNA extracted from pleural effusion can accurately detect important cancer genes and drug resistance mechanisms. 

These findings will help physicians select more effective treatments and improve diagnostic tools for advanced-stage NSCLC patients.