PPARγ通过Th17偏振和CEBPA/IL-17C信号加速OSCC的进展
Ying Wang1, Jing Liang1, Shiyu Zhang1
1State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Research Unit of Oral Carcinogenesis and Management, Chinese Academy of Medical Sciences, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Journal of cancer research and clinical oncology
|September 15, 2025
概括
这项研究揭示了氧酶增殖器激活受体玛 (PPARγ) 通过促进炎症Th17细胞分化来驱动口腔癌的进展. 向PPARγ提供了一种潜在的策略,可以抑制瘤生长,并增强口腔状细胞癌 (OSCC) 的免疫疗法.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 口腔状细胞癌 (OSCC) 具有侵入性,治疗效果有限,特别是在晚期.
- 瘤微环境 (TME) 由于其免疫抑制性,在OSCC发育和治疗耐药性方面发挥着至关重要的作用.
- 氧酶增殖器激活受体玛 (PPARγ) 在瘤生物学中起着复杂的作用,影响各种细胞过程.
研究的目的:
- 调查PPARγ在调节瘤微环境 (TME) 在口腔状细胞癌 (OSCC) 中的作用.
- 确定PPARγ对OSCC进展和TME内的免疫细胞分化的影响.
主要方法:
- 使用4-尼托基诺林-1-氧化物 (4NQO) 诱导的OSCC模型通过免疫组织化学 (IHC) 评估PPARγ表达.
- 采用批量和单细胞RNA测序 (RNA-seq) 来识别PPARγ介导的瘤促进机制.
- 在体外进行OSCC细胞和CD4+T细胞的共同培养,以及体内皮下瘤模型,以研究PPARγ对Th17细胞分化的影响.
主要成果:
- 抑制PPARγ显著降低OSCC细胞增殖,并降低了关键IL-17通路基因,包括IL-17C.
- 发现PPARγ通过转录上调CEBPA/IL-17C/IL-17A信号通路来促进Th17细胞分化.
- 在细胞和动物实验中,用GW9662对PPARγ的药理抑制损害了Th17细胞极化,并降低了CEBPA,IL-17C和IL-17A的表达.
结论:
- 确定了一种涉及PPARγ/CEBPA/IL-17C/IL-17A的新型信号轴,该轴驱动Th17细胞分化,并导致OSCC中的瘤相关炎症.
- 向PPARγ成为抑制瘤进展和调节OSCC中免疫微环境的有希望的治疗策略.
- 这项研究为管理口腔状细胞癌的潜在免疫治疗方法提供了新的见解.
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