2018年7月18日 · In this Review, we provide an overview of the control of CD4 + T cell immunity by members of the HDAC family. We first summarize the basic principles and known functions of HDACs as histone...

HDAC在各种实体瘤中过表达或过度活跃，并抑制肿瘤抑制基因的表达，从而导致增殖不受控制以及对细胞修复机制和细胞凋亡不敏感。 因此，HDAC也是开发特异性抗癌药物的潜在靶点。 大多数HDAC抑制剂具有三种主要药效团： Cap基团 （表面识别基团）、 ZBG （锌结合基团）以及连接Cap基团和ZBG的 Linker，其结构如下图所示。 根据结构类型， HDAC抑制剂可分为四类： 羟肟酸类 、 环四肽类 、苯甲酰胺类和 脂肪酸类。 目前已知FDA批准的HDAC抑制剂包括 …

Multi-omics analyses reveal that HDAC1 controls expression, chromatin accessibility, and histone acetylation of the transcription factors IRF4, IRF8, and SPIB required for efficient development of cDC2 subsets.

2016年8月15日 · Using the HDACi romidepsin in vivo, we observed increased chemokine expression, enhanced T-cell infiltration, and T-cell-dependent tumor regression. Importantly, romidepsin significantly enhanced the response to PD-1 blockade immunotherapy in multiple lung tumor models, including nearly complete rejection in two models.

2024年4月23日 · Here, we identify class I histone deacetylase inhibitors (HDACi) as boosters of CAR-T cell function by high-throughput screening of chromatin-modifying drugs, in which M344 and chidamide enhance memory maintenance and resistance to exhaustion of CAR-T cells that induce sustained antitumor efficacy both in vitro and in vivo.

2024年9月1日 · HDAC complexes play vital roles in the regulation of key biological processes such as transcription, replication, and DNA repair. Moreover, deregulated HDAC complex function is implicated in human diseases including cancer. Therapeutic strategies targeting HDAC complexes are being sought actively.

The use of both genetic KOs and class I HDAC specific inhibitors has highlighted the importance of HDAC1/2 in removing acetylation from high stoichiometry sites on histone tails ... Unpaired t-tests were then conducted using GraphPad Prism to determine if there were any significant differences in viability based on the HDAC1/2 status of the cells.

2024年4月4日 · Class I HDACi enhance persistence and in vivo antitumor efficacy of CAR-T cells. Epigenetic modification shapes differentiation trajectory and regulates the exhaustion state of chimeric antigen receptor T (CAR-T) cells. Limited efficacy induced by terminal exhaustion closely ties with intrinsic transcriptional regulation.

2025年2月15日 · Several HDAC inhibitors (HDACis), such as vorinostat, romidepsin, and belinostat, have received approval for the treatment of cutaneous T-cell lymphoma or peripheral T-cell lymphoma, with pracinostat also being granted orphan drug status for the treatment of AML [17, 18]. However, due to the high toxicity and limited efficacy of these pan ...

Histone Deacetylase 3 (HDAC3) function in vivo is nuanced and directed in a tissue-specific fashion. The importance of HDAC3 in Kras mutant lung tumors has recently been identified, but HDAC3 function in this context remains to be fully elucidated. Here, we identified HDAC3 as a lung tumor cell–intrinsic transcriptional regulator of the tumor immune microenvironment.