From Tumour to Bloodstream: Advancing PD-L1 Testing With Liquid Biopsies in Non-Small Cell Lung Cancer
R Leporati1,2, V Callegari2, A Ancora2
1Division of Medical Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy.
Abstract:
Immune checkpoint inhibitors (ICIs) have revolutionised the treatment landscape of non-small cell lung cancer (NSCLC) without actionable genomic alterations by opening new possibilities for treatment. However, the predictive value of Programmed Death-Ligand 1 (PD-L1) expression assessed by immunohistochemistry (IHC) is quite modest, leaving many patients without optimal benefit from ICIs. To address this gap, liquid biopsy is gaining momentum as a promising tool to complement tissue-based PD-L1 assessment. Liquid biopsy, which entails the analysis of circulating tumour cells (CTCs), extracellular vesicles (EVs), circulating tumour DNA (ctDNA), and other biomarkers, offers a non-invasive approach for tracking disease evolution and interactions with the immune system. We conducted a narrative review to explore the potential of liquid biopsy in enhancing patient selection for ICIs, its predictive and prognostic value in advanced NSCLC, and the associated technical and clinical implications. By highlighting recent advancements and ongoing research efforts, we underscore the critical role of liquid biopsy in driving precision immuno-oncology. Establishing robust, reproducible methods for PD-L1 assessment through liquid biopsy is essential for translating this approach into clinical practice, with the potential to overcome the limitations of tissue-based assays and better individualise immunotherapy strategies in NSCLC.
Insights
Liquid biopsy shows promise for improving patient selection for immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). This non-invasive approach may overcome limitations of current tissue-based tests for Programmed Death-Ligand 1 (PD-L1) assessment.
Area of Science:
- Oncology
- Immunology
- Molecular Diagnostics
Background:
- Immune checkpoint inhibitors (ICIs) have transformed non-small cell lung cancer (NSCLC) treatment, particularly for tumors lacking actionable genomic alterations.
- Current reliance on immunohistochemistry (IHC) for Programmed Death-Ligand 1 (PD-L1) assessment has modest predictive value, limiting optimal ICI benefit for many patients.
Purpose of the Study:
- To explore the potential of liquid biopsy as a complementary tool to tissue-based PD-L1 assessment in NSCLC.
- To review the predictive and prognostic value of liquid biopsy in advanced NSCLC for patient selection and treatment individualization.
- To discuss the technical and clinical implications of liquid biopsy in precision immuno-oncology.
Main Methods:
- A narrative review of recent advancements and ongoing research in liquid biopsy for NSCLC.
- Analysis of biomarkers such as circulating tumor cells (CTCs), extracellular vesicles (EVs), and circulating tumor DNA (ctDNA).
- Evaluation of liquid biopsy's role in tracking disease evolution and immune system interactions.
Main Results:
- Liquid biopsy offers a non-invasive method for assessing biomarkers like PD-L1, potentially enhancing patient selection for ICIs.
- Emerging evidence suggests liquid biopsy can provide predictive and prognostic information in advanced NSCLC.
- Advancements in liquid biopsy techniques are crucial for driving precision immuno-oncology.
Conclusions:
- Liquid biopsy holds significant potential to overcome the limitations of tissue-based PD-L1 assays in NSCLC.
- Establishing standardized and reproducible liquid biopsy methods is essential for clinical implementation.
- This approach promises to enable more individualized immunotherapy strategies for NSCLC patients.


