Park Jeenah, Thomas Scott, Munster Pamela N
Department of Medicine, Hematology/Oncology Division, University of California, San Francisco, CA 94115, USA.
Epigenomics. 2015;7(4):641-52. doi: 10.2217/epi.15.16.
Understanding the contribution of dysregulated gene silencing to epigenomic alterations in cancer development provides the rationale for the use of epigenetic modulators, such as histone deacetylase (HDAC) inhibitors, in cancer therapy. HDAC inhibitors have been approved as single agents for cutaneous and peripheral T-cell lymphoma and have shown promising activity in reversing therapy resistance in other tumor types. The effects of HDAC inhibitors on immune modulation have created a recent interest in their potential role in immunotherapy. This review describes the current understanding on integrating HDAC inhibitors into various immunotherapeutic approaches, such as cancer vaccines, adoptive T-cell transfer and immune checkpoint inhibitors. Furthermore, it summarizes promising treatment strategies in epigenetic immune priming from clinical trials that are currently underway.
了解基因沉默失调对癌症发展过程中表观基因组改变的作用,为在癌症治疗中使用表观遗传调节剂(如组蛋白脱乙酰酶(HDAC)抑制剂)提供了理论依据。HDAC抑制剂已被批准作为治疗皮肤和外周T细胞淋巴瘤的单一药物,并在逆转其他肿瘤类型的治疗耐药性方面显示出有前景的活性。HDAC抑制剂对免疫调节的作用引发了近期对其在免疫治疗中潜在作用的关注。本综述描述了目前关于将HDAC抑制剂整合到各种免疫治疗方法(如癌症疫苗、过继性T细胞转移和免疫检查点抑制剂)中的认识。此外,它总结了目前正在进行的临床试验中表观遗传免疫启动方面有前景的治疗策略。