Synergistic Integration of HDAC Inhibitors and Individualized Neoantigen Therapy (INT): A Next-Generation Combinatorial Approach for Cancer Immunotherapy

BACKGROUND: Cancer immunotherapy has advanced, yet therapeutic resistance and low response rates remain problematic. This study explores histone deacetylase inhibitors (HDACis) as adjuvants for cancer vaccines to enhance anti-tumor immunity and overcome these challenges. METHODS: A comprehensive review of relevant literature was conducted. Studies on the immunomodulatory mechanisms of HDACis, their effects on Individualized neoantigen therapy (INT), and clinical applications were analyzed. RESULTS: HDACis enhance anti-tumor immunity through multiple mechanisms. They activate endogenous retroelements, expanding the "antigen repository". HDACis also upregulate MHC class I and II molecules, enhance the antigen processing machinery, improve MHC-I complex stability, and remodel the tumor immune microenvironment. Early clinical trials of HDACis combined with peptide vaccines show promising safety and immunological responses. However, challenges exist, such as HDACi-mediated PD-L1 regulation, optimal sequencing strategies, and biomarker development. CONCLUSIONS: The combination of HDACis and cancer vaccines has significant potential in cancer immunotherapy. Despite challenges, it offers a new approach to overcome tumor heterogeneity and immune evasion, especially for patients with limited treatment options. Further research on toxicity management, triple-drug combinations, biomarker identification, and delivery systems is needed to fully realize its clinical benefits.