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空间转录学揭示了托代谢限制了内口腔三级淋巴体结构的成熟

Zhonghui Tang¹, Yinqi Bai², Qi Fang³

¹Advanced Medical Technology Center, The First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.

|April 4, 2025

概括

肝癌中的三级淋巴体结构 (TLS) 可能是不成熟的. 准托代谢促进TLS成熟,增强抗PD-1免疫疗法和瘤控制.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
系统生物学系统生物学

背景情况:

三级淋巴体结构 (TLS) 是瘤中的免疫细胞聚合物,与更好的癌症结局和免疫疗法的有效性有关.
影响TLS成熟的发育途径和因素仍然不完全理解,特别是在肝细胞癌 (HCC) 中.

研究的目的:

使用空间转录学,在HCC的不同成熟阶段全面描述TLS及其微环境.
确定不成熟TLS的不同发育轨迹及其对免疫治疗的功能影响.

主要方法:

在HCC中,对TLS及其周围微环境的近单细胞空间转录基因映射.
基于发展轨迹的不成熟TLS的分类,分为"符合"和"偏离"亚型.
在体内实验涉及抑制托代谢和与抗PD-1疗法的结合.

主要成果:

未成熟的TLS被分为符合型和偏离型,符合型TLS在支持免疫治疗方面与成熟的TLS具有功能相似性.
由恶性细胞驱动的富含托的代谢微环境被确定为促进TLS成熟偏差的关键因素.
抑制托代谢增强了内TLS成熟,改善了瘤控制,并与抗PD-1免疫疗法协同作用.

结论:

符合的TLS对免疫疗法反应具有功能相关性,而偏离的TLS则没有.
调节瘤微环境,特别是通过准托代谢,可以促进TLS成熟.
增强TLS成熟是一种有前途的治疗策略,可以改善接受免疫治疗的HCC患者的抗瘤免疫力和临床结果.

关键词:

成熟成熟成熟成熟.空间转录学空间转录学三级淋巴状结构的第三级淋巴状结构托的代谢过程

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