PD-L1 detection on circulating tumor-derived extracellular vesicles (T-EVs) from patients with lung cancer
Fei Wu1,2, Yanzi Gu3, Bin Kang1,2
1Fudan University Shanghai Cancer Center-Institut Mérieux Laboratory, Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China.
Background:
Recent breakthroughs in therapies with immune checkpoint inhibitors (ICIs) have revolutionized the treatment of lung cancer. However, only 15-25% of patients respond to the ICIs therapy, and methods to identify those responsive patients are currently a hot research topic. PD-L1 expression measured on tumor tissues using immunohistochemistry (IHC) was approved as one of the companion diagnostic methods, but it is invasive and cannot be used to monitor dynamic changes in PD-L1 expression during treatments.
Methods:
In this study, we developed an Epcam-PD-L1 extracellular vesicle (EV) detection prototype using the Simoa platform. This assay detected PD-L1 expression levels on tumor-derived exosomes from the lung cancer cell lines A549 and SK-MES1. In addition, 35 plasma samples from patients with lung cancer were tested with this assay and the results were compared to the tissue PD-L1 expression levels represented by the tumor proportion score (TPS).
Results:
PD-L1 TPS-positive patients (≥1% IHC TPS) had significantly higher Simoa Epcam-PD-L1 signals than TPS-negative patients (<1% IHC TPS, P=0.026). The Simoa Epcam-PD-L1 area under curve (AUC) reached 0.776, with a sensitivity of 92.86% and a specificity of 71.43%. When PD-L1 TPS-positive patients were defined as having an IHC TPS ≥10%, the greatest difference in Epcam-PD-L1 signals was observed between IHC TPS-positive and IHC TPS-negative groups (P=0.0024) and the Simoa Epcam-PD-L1 AUC reached 0.832. Finally, the Spearman's correlation coefficient showed a significant correlation between the TPS and Simoa Epcam-PD-L1 signals (0.428, P=0.0104).
Conclusions:
Based on our results, our Simoa Epcam-PD-L1 EV detection assay is a potential liquid biopsy method to predict the PD-L1 expression level in patients with lung cancer.
Insights
A new Simoa assay detects PD-L1 expression on extracellular vesicles in lung cancer patients. This liquid biopsy method shows promise for predicting treatment response to immune checkpoint inhibitors.
Area of Science:
- Oncology
- Immunotherapy
- Biomarker Discovery
Background:
- Immune checkpoint inhibitors (ICIs) have transformed lung cancer treatment, but patient response rates remain low (15-25%).
- Identifying ICI responders is crucial; current PD-L1 expression testing via immunohistochemistry (IHC) on tumor tissue is invasive and lacks dynamic monitoring.
- There is a need for non-invasive methods to assess PD-L1 expression and predict ICI therapy outcomes.
Purpose of the Study:
- To develop and evaluate a novel assay for detecting PD-L1 expression on extracellular vesicles (EVs) in lung cancer patients.
- To assess the correlation between EV-based PD-L1 detection and tissue-based PD-L1 expression (tumor proportion score, TPS).
- To determine the potential of this assay as a liquid biopsy for predicting ICI response.
Main Methods:
- Developed an Epcam-PD-L1 extracellular vesicle (EV) detection prototype using the Simoa platform.
- Tested the assay on PD-L1 expression levels on tumor-derived exosomes from lung cancer cell lines (A549, SK-MES1).
- Analyzed 35 plasma samples from lung cancer patients, comparing Simoa Epcam-PD-L1 signals with tissue PD-L1 (IHC TPS).
Main Results:
- Simoa Epcam-PD-L1 signals were significantly higher in PD-L1 TPS-positive patients (≥1% IHC TPS) compared to TPS-negative patients (P=0.026).
- The assay achieved an AUC of 0.776 (sensitivity 92.86%, specificity 71.43%) for ≥1% IHC TPS.
- When defining PD-L1 positivity as ≥10% IHC TPS, the AUC increased to 0.832, with a significant difference observed (P=0.0024).
- A significant positive correlation was found between Simoa Epcam-PD-L1 signals and TPS (Spearman's correlation coefficient=0.428, P=0.0104).
Conclusions:
- The developed Simoa Epcam-PD-L1 EV detection assay shows potential as a non-invasive liquid biopsy method.
- This assay can effectively predict PD-L1 expression levels in lung cancer patients.
- It may aid in selecting patients likely to benefit from ICI therapies.
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