The Role of PD-L1 in Lung Cancer: From Biology to Clinical Application

Lung cancer remains the primary cause of cancer-related mortality worldwide and is mainly classified into non-small cell lung cancer, which accounts for approximately 85% of cases, and small cell lung cancer, representing about 15%. In recent years, major therapeutic progress has been achieved through the development of immunotherapies, particularly immune checkpoint inhibitors targeting the PD-1/PD-L1 axis. These treatments aim to restore antitumor immune responses by blocking the interaction between PD-1, expressed on T lymphocytes, and its ligand PD-L1, which can be overexpressed by tumor cells. Under physiological conditions, PD-L1 plays an essential role in maintaining immune tolerance; however, its dysregulated expression in cancer contributes to immune evasion. The level of PD-L1 expression assessed by immunohistochemistry has emerged as a key predictive biomarker for patient response to immunotherapy. Nevertheless, PD-L1 expression is heterogeneous and influenced by multiple biological, clinical and technical factors. In this review, we aim to summarize the biological role of PD-L1 in lung cancer, discuss its expression patterns and regulatory mechanisms, describe current assessment methods, and highlight its clinical relevance in guiding immunotherapy strategies.