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功能性遗传查揭示了指导瘤相关巨细胞分子表型的关键途径

Youxue Lu¹, Ce Luo², Lanxiang Huang³

¹Tsinghua University, Beijing, Beijing, China.

Cancer immunology research

|September 4, 2025

概括

乳酸和PGE2等瘤衍生因素形成了多种瘤相关的巨细胞 (TAM) 表型. 重新编程TAM可以通过促进T细胞透来增强抗癌免疫力.

科学领域:

免疫学
癌症生物学
瘤微环境

背景情况:

与瘤相关的巨细胞表现出显著的功能多样性.
TAM偏振的分子驱动因素在很大程度上是未知的.
了解TAM异质性对于癌症免疫治疗至关重要.

研究的目的:

确定调节TAM两极化的关键瘤衍生因素.
阐明TAM表型多样化的基础机制.
探索TAM重编程的治疗策略.

主要方法:

在原始巨细胞中进行CRISPR选.
对瘤衍生因素 (乳酸,PGE2,GM-CSF) 的分析.
基因表达调节的染色体水平研究.

主要成果:

乳酸和PGE2协同作用,诱导血管生成程序并抑制GM-CSF驱动的MHC-II表达.
不同的TAM表型 (亲血管性,MHC- II+) 在人类癌症中保持存在,并且在空间上分离.
通过ADAR无活化,TAMs会转变为对干扰素有反应的状态,从而促进CD8+ T细胞的透.

结论:

发现由瘤微环境因素驱动的TAM两极分化的保存机制.
证明TAM重编程可以增强抗癌免疫力.
提供了针对TAM改善癌症免疫疗法的新疗法.

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