Advances in Neoantigen-based Immunother apy for Head and Neck Squamous Cell Car cinoma (HNSCC): A Compr ehensive Review

Manzhu Jiang¹Jiefu Li²Jianhua Wei³Xuerong Yang^1*Weiqi Wang^3*

• ¹College of Life Sciences, Shandong Agricultural University, Tai'an, Shandong Province, China
• ²Guangzhou National Laboratory, Guangzhou, Guangdong, China
• ³School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi Province, China

Head and Neck Squamous Cell Carcinoma (HNSCC), ranking among the six most prevalent malignancies worldwide, is characterized by significant heterogeneity. Conventional monotherapeutic approaches, including surgical intervention, radiotherapy, and chemotherapy, often fail to achieve complete tumor cell elimination, consequently leading to disease recurrence and metastatic progression. In this context, personalized immunotherapeutic strategies, particularly cancer vaccines and immune checkpoint inhibitors, have emerged as promising therapeutic modalities for patients with recurrent/metastatic (R/M) HNSCC. Neoantigens, which exhibit selective expression in tumor tissues while remaining absent in normal tissues, have garnered considerable attention as novel targets for HNSCC personalized immunotherapy. However, the marked heterogeneity of HNSCC, coupled with patient-specific HLA variations, necessitates precise technical identification and evaluation of neoantigens at the individual level-a significant contemporary challenge. This comprehensive review systematically explores the landscape of neoantigen-based immunotherapy in HNSCC, including neoantigen sources, screening strategies, identification methods, and their clinical applications. Additionally, it evaluates the therapeutic potential of combining neoantigen-based approaches with other immunotherapeutic modalities, particularly immune checkpoint inhibitors, providing valuable insights for future clinical practice and research directions in HNSCC treatment.