Advances in immunotherapy combination strategies and biomarkers for locally advanced nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is a distinct type of head and neck malignancy characterized by unique geographical and ethnic distribution patterns, with its pathogenesis and progression closely associated with Epstein-Barr virus (EBV) infection. Despite significant advancements in multimodal treatment strategies incorporating concurrent chemoradiotherapy, disease recurrence and metastasis continue to pose substantial clinical challenges, particularly in the management of locally advanced nasopharyngeal carcinoma (LA-NPC). In recent years, remarkable progress has been made in immunotherapeutic approaches for LA-NPC, with immune checkpoint inhibitors (ICIs) targeting the programmed cell death-1 (PD-1) and its ligand PD-L1 axis emerging as a transformative therapeutic strategy, demonstrating favorable antitumor efficacy in clinical settings. Notably, EBVpositive patients exhibit enhanced sensitivity to immunotherapy, which is closely related to their unique tumor immune microenvironment characteristics. This article provides a comprehensive review of recent advancements in immunotherapy for LA-NPC, focusing on the following key areas: EBV-associated immune microenvironment characteristics, novel timing-optimized models, low-dose radiotherapy combinations, tumor microenvironment modulation, and novel immunotherapeutic technologies. Additionally, it also assesses the clinical prospects and challenges, aiming to offer strategic directions for future research in immunotherapy for LA-NPC.