Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Gene. 2023 Nov 15;885:147704. doi: 10.1016/j.gene.2023.147704. Epub 2023 Aug 11.
The role of histone deacetylases (HDACs) in the tumor immune microenvironment of gynecologic tumors remains unexplored. We integrated data from The Cancer Genome Atlas and Human Protein Atlas to examine HDAC expression in breast, cervical, ovarian, and endometrial cancers. Elevated HDAC expression correlated with poor prognosis and highly malignant cancer subtypes. Gene Set Enrichment Analysis revealed positive associations between HDAC expression and tumor proliferation signature, while negative associations were found with tumor inflammation signature. Increased HDAC expression was linked to reduced infiltration of natural killer (NK), NKT, and CD8 T cells, along with negative associations with the expression of PSMB10, NKG7, CCL5, CD27, HLA-DQA1, and HLA-DQB1. In a murine 4T1 breast cancer model, treatment with suberoylanilide hydroxamic acid (SAHA; HDAC inhibitor) and PD-1 antibody significantly inhibited tumor growth and infiltration of CD3 and CD8 T cells. Real-time polymerase chain reaction revealed upregulated expressions of Psmb10, Nkg7, Ccl5, Cd8a, Cxcr6, and Cxcl9 genes, while Ctnnb1 and Myc genes were inhibited, indicating tumor suppression and immune microenvironment activation. Our study revealed that HDACs play tumor-promoting and immunosuppressive roles in gynecologic cancers, suggesting HDAC inhibitors as potential therapeutic agents for these cancers.
组蛋白去乙酰化酶（HDACs）在妇科肿瘤的肿瘤免疫微环境中的作用仍未被探索。我们整合了来自癌症基因组图谱和人类蛋白质图谱的数据，以检查乳腺癌、宫颈癌、卵巢癌和子宫内膜癌中的 HDAC 表达。HDAC 表达升高与预后不良和高度恶性的癌症亚型相关。基因集富集分析显示 HDAC 表达与肿瘤增殖特征呈正相关，而与肿瘤炎症特征呈负相关。HDAC 表达增加与自然杀伤（NK）、NKT 和 CD8 T 细胞浸润减少有关，与 PSMB10、NKG7、CCL5、CD27、HLA-DQA1 和 HLA-DQB1 的表达呈负相关。在 4T1 乳腺癌小鼠模型中，用丁酸钠（SAHA；HDAC 抑制剂）和 PD-1 抗体治疗显著抑制了肿瘤生长和 CD3 和 CD8 T 细胞的浸润。实时聚合酶链反应显示 Psmb10、Nkg7、Ccl5、Cd8a、Cxcr6 和 Cxcl9 基因的表达上调，而 Ctnnb1 和 Myc 基因受到抑制，表明肿瘤抑制和免疫微环境激活。我们的研究表明，HDACs 在妇科癌症中发挥促肿瘤和免疫抑制作用，提示 HDAC 抑制剂可能是这些癌症的潜在治疗药物。
