Core regulatory mechanisms of the PD-L1 axis and clinical strategies for immune escape and immunotherapy response in nasopharyngeal carcinoma

The programmed death ligand 1 (PD-L1) axis serves as a pivotal pathway mediating tumor immune escape, with a unique and complex role in nasopharyngeal carcinoma (NPC). Recent advances in ICIs targeting the PD-1/PD-L1 pathway have significantly improved the prognosis of patients with recurrent or metastatic NPC. However, the clinical benefits exhibit substantial heterogeneity, underscoring the need to elucidate the underlying regulatory mechanisms. This review systematically summarizes the multilayered regulation of PD-L1 expression in NPC, encompassing genomic, transcriptional, epigenetic, and post-translational modifications. Special emphasis is placed on the influence of Epstein-Barr virus (EBV)-associated signaling, inflammatory cytokines, and therapeutic interventions on the dynamic modulation of PD-L1. Furthermore, the intrinsic relationship between dynamic PD-L1 expression changes and the efficacy and resistance mechanisms of ICIs is explored. Integrating the latest clinical trial data, we critically evaluate the progress and challenges of combining PD-1/PD-L1 inhibitors with chemotherapy, radiotherapy, and targeted therapies. Finally, we propose future directions for personalized immunotherapy strategies based on PD-L1 regulatory networks and biomarker development, aiming to optimize immune-based treatment paradigms for NPC and provide theoretical foundations and practical guidance for clinical management.