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 rev...
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| Format: | Article |
| Language: | English |
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MDPI AG
2025-05-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/13/6/550 |
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| author | Rui Han Huiling Zhou Baoqing Peng Shasha Yu Jiajie Zhu Jiaojiao Chen |
| author_facet | Rui Han Huiling Zhou Baoqing Peng Shasha Yu Jiajie Zhu Jiaojiao Chen |
| author_sort | Rui Han |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ebe47c1100064450880dc2f0b72bcc3a |
| institution | Kabale University |
| issn | 2076-393X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj-art-ebe47c1100064450880dc2f0b72bcc3a2025-08-20T03:26:56ZengMDPI AGVaccines2076-393X2025-05-0113655010.3390/vaccines13060550Synergistic Integration of HDAC Inhibitors and Individualized Neoantigen Therapy (INT): A Next-Generation Combinatorial Approach for Cancer ImmunotherapyRui Han0Huiling Zhou1Baoqing Peng2Shasha Yu3Jiajie Zhu4Jiaojiao Chen5Department of Chinese Medicine Oncology, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, ChinaDepartment of Chinese Medicine Oncology, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, ChinaDepartment of Chinese Medicine Oncology, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, ChinaDepartment of Chinese Medicine Oncology, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, ChinaDepartment of Gastroenterology, Tongde Hospital of Zhejiang Province, Hangzhou 310012, ChinaDepartment of Chinese Medicine Oncology, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, ChinaBackground: 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.https://www.mdpi.com/2076-393X/13/6/550histone deacetylase inhibitorsindividualized neoantigen therapy (INT)immunotherapyantigen presentationtumor microenvironment |
| spellingShingle | Rui Han Huiling Zhou Baoqing Peng Shasha Yu Jiajie Zhu Jiaojiao Chen Synergistic Integration of HDAC Inhibitors and Individualized Neoantigen Therapy (INT): A Next-Generation Combinatorial Approach for Cancer Immunotherapy Vaccines histone deacetylase inhibitors individualized neoantigen therapy (INT) immunotherapy antigen presentation tumor microenvironment |
| title | Synergistic Integration of HDAC Inhibitors and Individualized Neoantigen Therapy (INT): A Next-Generation Combinatorial Approach for Cancer Immunotherapy |
| title_full | Synergistic Integration of HDAC Inhibitors and Individualized Neoantigen Therapy (INT): A Next-Generation Combinatorial Approach for Cancer Immunotherapy |
| title_fullStr | Synergistic Integration of HDAC Inhibitors and Individualized Neoantigen Therapy (INT): A Next-Generation Combinatorial Approach for Cancer Immunotherapy |
| title_full_unstemmed | Synergistic Integration of HDAC Inhibitors and Individualized Neoantigen Therapy (INT): A Next-Generation Combinatorial Approach for Cancer Immunotherapy |
| title_short | Synergistic Integration of HDAC Inhibitors and Individualized Neoantigen Therapy (INT): A Next-Generation Combinatorial Approach for Cancer Immunotherapy |
| title_sort | synergistic integration of hdac inhibitors and individualized neoantigen therapy int a next generation combinatorial approach for cancer immunotherapy |
| topic | histone deacetylase inhibitors individualized neoantigen therapy (INT) immunotherapy antigen presentation tumor microenvironment |
| url | https://www.mdpi.com/2076-393X/13/6/550 |
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