单核和空间转录基因组概况描绘了肝细胞癌在肝动脉输液化疗后的多细胞生态系统
YeXing Huang1, ZeFeng Du1, ZhiCheng Lai1
1Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, Guangdong Provincial Clinical Research Center for Cancer, State Key Laboratory of Oncology in South China, Guangzhou, 510060, P. R. China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|December 17, 2024
概括
肝动脉输液化疗 (HAIC) 重塑肝细胞癌 (HCC) 瘤微环境,增强免疫细胞活性和三级淋巴体结构. 特定的CD8+ T细胞显示出抗瘤潜力,作为HAIC疗效的生物标志物.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
背景情况:
- 肝细胞癌 (HCC) 是一种主要的肝癌,治疗选择有限.
- 肝动脉输液化疗 (HAIC) 是治疗HCC的一个有前途的策略.
- 在HAIC之后的治疗后瘤微环境仍然不太了解.
研究的目的:
- 在HAIC治疗后对HCC的多细胞生态系统进行表征.
- 在HAIC后识别免疫细胞变化和细胞通信模式.
- 探索第三级淋巴细胞结构 (TLS) 和特定的T细胞群体对HAIC的反应中的作用.
主要方法:
- 集成的单核RNA测序和空间转录组学.
- 对从未接受过治疗的和经过HAIC HCC 患者的瘤样本的分析.
- 免疫细胞亚型,细胞通信和TLS形成的表征.
主要成果:
- 在HAIC后观察到CD4+ T,CD20+ B和树突细胞种群的增加.
- 治疗HAIC促进了三级淋巴体结构 (TLS) 的形成.
- 鉴定出具有抗瘤功能的中间耗尽的CD8+T细胞 (PD-1+CD8+Tex-int) 的扩张,在TLS内累积.
结论:
- HAIC显著改变HCC瘤生态系统,增强免疫细胞透和通信.
- 通过HAIC促进TLS的形成,并作为免疫细胞相互作用的利基.
- PD-1+CD8+Tex-int细胞代表了HCC中HAIC治疗反应的潜在生物标志物.
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