From Tumour to Bloodstream: Advancing PD-L1 Testing With Liquid Biopsies in Non-Small Cell Lung Cancer.

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.