转录因子Zhx2是一个检查点,可以编程巨细胞两极分化和抗瘤反应
Siyu Tan1,2, Zehua Wang2,3, Na Li2
1Department of General Surgery, Qilu Hospital, Shandong University, Jinan, China.
Cell death and differentiation
|August 15, 2023
概括
指和家庭盒2 (Zhx2) 调节巨细胞的两极分化. 瘤相关巨细胞 (TAMs) 中Zhx2的损失促进癌症的进展,提供了一个潜在的免疫治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
- 分子生物学分子生物学
背景情况:
- 与瘤相关的巨细胞 (TAMs) 促进癌症的进展.
- 重编程TAM是一种潜在的免疫疗法策略.
- 指和家庭盒2 (Zhx2) 参与巨细胞代谢编程.
研究的目的:
- 调查Zhx2在巨细胞极化和TAM重编程中的作用.
- 探索 Zhx2 在瘤微环境 (TME) 中的功能.
主要方法:
- 鼠肝瘤模型具有髓状细胞特异性Zhx2删除.
- 对巨细胞两极分化的分析 (LPS,IL-4,TME刺激).
- 在肝细胞癌 (HCC) 患者样本中分析ZHX2表达.
- 涉及Zhx2,NF-κB p65和Irf1促进体结合的机制研究.
主要成果:
- 删除zhx2抑制了亲炎性巨细胞的两极分化,但促进了抗炎/亲瘤的表型.
- TME因子,特别是乳酸,减少了TAMs中的Zhx2表达,推动了前瘤功能.
- 在TAMs中减少ZHX2表达与HCC患者生存率差相关.
- Zhx2与Irf1促进体结合,调节其在巨细胞中的转录.
结论:
- Zhx2控制着巨细胞极化和TAM重编程.
- 由TME因素降低zhx2的调节促进了癌症的进展.
- Zhx2是基于巨细胞的癌症免疫治疗的潜在治疗标.
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