# Advances in neoantigen-based immunotherapy for head and neck squamous cell carcinoma: a comprehensive review

## TL;DR

This review explores how neoantigen-based immunotherapy could improve treatment for head and neck cancer, focusing on personalized approaches and challenges.

## Contribution

The paper provides a comprehensive review of neoantigen-based immunotherapy strategies for HNSCC, emphasizing personalized approaches and combination therapies.

## Key findings

- Neoantigens are promising targets for personalized immunotherapy in HNSCC due to their tumor-specific expression.
- Combining neoantigen-based therapies with immune checkpoint inhibitors may enhance treatment outcomes.
- HLA variations and tumor heterogeneity pose significant challenges in neoantigen identification and application.

## Abstract

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.