Advances and challenges in immunotherapy for locally advanced nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a prevalent malignant tumor of the head and neck, with approximately 70 % of patients being diagnosed at a locally advanced stage. Despite the responsiveness to radiotherapy and chemotherapy, the 5-year survival rate of locally advanced NPC (LANPC) remains at approximately 80 %. Hence, there is an urgent need for novel treatment strategies to improve the prognosis of patients with LANPC. Numerous studies have illustrated the efficacy of immune checkpoint inhibitors (ICIs) in recurrent/metastatic NPC. Hence, the potential of immunotherapy for LANPC is under investigation. Using the Web of Clinical Trials, we identified 84 relevant trials exploring immunotherapy for NPC, encompassing 17 trials focusing on ICIs for LANPC. Preliminary findings from several trials suggest that adding ICIs into the primary treatment for LANPC significantly enhances the objective response rate and progression-free survival, with manageable safety profiles. However, the type, dosage, and timing of integration (induction phase, concurrent phase, and adjuvant phase) of ICIs into standard primary treatment of LANPC varies among these trials and further researches are warranted. This review provides an overview of immunotherapy principles in NPC, discusses recent advances and challenges associated with ICIs in the primary treatment for LANPC derived from published and ongoing clinical trials, and outlines the current landscape of other immunotherapies in LANPC, such as adoptive cell therapy, immunomodulatory agents, and tumor vaccines in LANPC. These insights aim to inform clinical practice and guide future researches.