膀癌进展中的上皮细胞多样性和免疫重塑:从单细胞转录组学的见解
Jianpeng Li1, Yunzhong Jiang1, Minghai Ma1
1Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
Journal of translational medicine
|January 30, 2025
概括
膀癌的进展涉及瘤微环境的显著变化,包括增加糖解和T细胞耗尽,这促进了免疫逃避. 针对这些途径为膀癌 (BC) 提供了新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 基因组学就是基因组学.
背景情况:
- 膀癌 (BC) 从非肌肉侵入性 (NMIBC) 到肌肉侵入性 (MIBC) 阶段的进展增加了疾病的严重程度.
- 瘤微环境 (TME) 在BC进展中至关重要,但其细胞和分子异质性尚未完全理解.
研究的目的:
- 在膀癌进展过程中描述TME的转录基因格局.
- 确定驱动BC进展和免疫逃避的关键细胞和分子变化.
主要方法:
- 11个BC样本的单细胞RNA测序 (4个NMIBC,4个MIBC,3个正常组织).
- 使用大量RNA-seq,免疫组织化学 (IHC) 和多重免疫光学验证.
主要成果:
- MIBC瘤细胞表现出增强的葡萄糖分解和降低的免疫信号 (化学因子,MHC-II),促进免疫逃避.
- 确定了一种T细胞耗尽通路 (CD8+ TCF7到CD8+ STMN1),损害了抗瘤免疫力.
- 巨细胞采用了一种亲瘤原型的表型,VEGFA+巨细胞促进了血管生成,树突细胞 (DC) 转化为LAMP3+DC,有助于免疫抑制.
结论:
- 膀癌进展的特征是TME变化,包括增强的糖解,T细胞疲劳和免疫细胞重编程.
- 这些变化促进了免疫逃避和瘤生长,突出了潜在的治疗点,如糖解和特定的免疫细胞群.
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