Navigating PD-L1 testing in immuno-oncology: analytical robustness, clinical validation, and the role of the VENTANA SP263 assay

INTRODUCTION: PD-L1 expression today represents a crucial biomarker in the selection of patients eligible for immune checkpoint inhibitor therapies (PD-1/PD-L1), particularly in tumors such as NSCLC, urothelial carcinoma, and TNBC. Its role in modulating immune response and the tumor microenvironment makes this topic of growing relevance in clinical oncological practice. AREAS COVERED: This review examines the most recent literature on histological and plasma PD-L1 expression, comparative studies between antibodies and IHC cutoffs, integration of liquid biopsy and new biomarkers (e.g. CPS, ctDNA). A targeted literature search was conducted using PubMed/MEDLINE, Scopus, and Web of Science, covering publications from January 2010 to March 2025. Meta-analyses and clinical studies related to TNBC, NSCLC, and urothelial carcinoma are included, with insights into therapeutic resistance and combination strategies. EXPERT OPINION: While SP263 demonstrates strong analytical performance and reproducibility, analytical concordance does not equate to clinical interchangeability. PD-L1 testing should remain assay-, tissue-, and indication-specific, supported by regulatory approval and clinical outcome data. Future integration of digital tools and multimodal biomarkers may improve standardization and predictive accuracy.