瘤免疫微环境的重塑和对HER2-阳性晚期胃癌中HER2-向治疗的反应
Lei Jiang1, Xingwang Zhao2, Yilin Li1
1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China.
IUBMB life
|December 21, 2023
概括
与抗HER2药物和免疫疗法的联合治疗增强了胃癌 (GC) 中的免疫细胞透. 特定的细胞相互作用,如NK细胞招募CD8+T细胞,是推动GC患者治疗益处的关键机制.
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:
- 与抗HER2药物和免疫疗法的联合治疗在胃癌 (GC) 中显示出有前途.
- 在GC中这些组合疗法的有效性背后的精确机制在很大程度上仍未被阐明.
- 了解瘤微环境 (TME) 调制对于优化抗HER2和免疫治疗策略至关重要.
研究的目的:
- 为了研究晚期胃癌 (GC) 抗HER2治疗后瘤微环境 (TME) 的变化.
- 阐明细胞对细胞通信网络和驱动治疗反应的分子机制.
- 确定潜在的生物标志物和治疗点,以提高GC中抗HER2和免疫疗法的疗效.
主要方法:
- 多重免疫组织化学被用于分析47名接受抗HER2治疗的晚期GC患者的TME变化.
- 单细胞RNA测序 (scRNA-seq) 在四个HER2-阳性GC基线样本上进行,以探索细胞间通信.
- 进行了空间分布分析,以评估与治疗益处相关的细胞-细胞相互作用评分.
主要成果:
- 与基线相比,抗HER2治疗导致自然杀手 (NK) 细胞,CD8+ T细胞和B淋巴细胞在响应者中的透增加.
- 在受益患者中,NK细胞和CD8+T细胞,B淋巴细胞和M2巨细胞,以及B淋巴细胞和调节性T细胞 (Tregs) 之间观察到显著更高的相互作用评分.
- scRNA-seq揭示NK细胞使用CCL3/CCL4-CCR5信号来招募CD8+T细胞,而B淋巴细胞通过不同的途径与M2巨细胞和Tregs相互作用 (分别是CD74-APP/COPA/MIF和TNF-FAS/ICOS/TNFRSR1B).
结论:
- 该研究确定了特定的免疫细胞相互作用和信号通路,作为GC中抗HER2治疗反应的关键调解者.
- 这些相互作用,包括NK细胞对CD8+T细胞的招募和M2巨细胞和Tregs的B细胞调节,对于克服免疫抵抗至关重要.
- 这些发现为指导抗HER2药物和免疫治疗在GC治疗中的联合应用提供了宝贵的见解.
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