Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Key Laboratory of Henan Province for Drug Quality and Evaluation, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China.
Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Key Laboratory of Henan Province for Drug Quality and Evaluation, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China; China Meheco Topfond PharmaceuticalCo., Ltd., Zhumadian 463000, PR China.
Bioorg Chem. 2021 Apr;109:104754. doi: 10.1016/j.bioorg.2021.104754. Epub 2021 Feb 20.
Tumor immunotherapy is currently subject of intense scientific and clinical developments. In previous decade, therapists used natural immune system from the human body to treat several diseases. Although tumor immune disease is a big challenge, combinatorial therapeutic strategy has been succeeded to show the clinical significance. In this context, we discuss the HDAC6 and tumor immune diseases relationship. Also, we summarized the current state of knowledge that based on the combination treatments of the HDAC6 inhibitors (HDAC6is) with antitumor immunomodulatory agents. We observed that, the combination therapies slow down the tumor immune diseases by blocking the aggresome and proteasome pathway. The combination therapy was able to reduce M2 macrophage and increasing PD-L1 blockade sensitivity. Most importantly, multiple combinations of HDAC6is with other agents may consider as potential strategies to treat tumor immune diseases, by reducing the side effects and improve efficacy for the future clinical development.
肿瘤免疫疗法目前是科学和临床发展的热点。在过去的十年中，治疗师利用人体的天然免疫系统来治疗多种疾病。尽管肿瘤免疫疾病是一个巨大的挑战，但联合治疗策略已经成功地显示出了临床意义。在这种情况下，我们讨论了 HDAC6 与肿瘤免疫疾病的关系。此外，我们总结了目前基于 HDAC6 抑制剂（HDAC6is）与抗肿瘤免疫调节剂联合治疗的知识现状。我们观察到，通过阻断聚集体和蛋白酶体途径，联合治疗可以减缓肿瘤免疫疾病的进展。联合治疗能够减少 M2 巨噬细胞并增加 PD-L1 阻断的敏感性。最重要的是，HDAC6is 与其他药物的多种组合可能被认为是治疗肿瘤免疫疾病的潜在策略，通过减少副作用和提高未来临床开发的疗效。
