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人体表皮生长因子-2 (HER2) 阳性食道腺癌中的瘤免疫微环境特征:比较分析和生物标志物研究

Charlotte I Stroes¹, Sybren L Meijer², Geert-Jan Creemers³

¹Amsterdam UMC, Location University of Amsterdam, Department of Medical Oncology, Amsterdam, the Netherlands; Amsterdam UMC, Location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory of Experimental Oncology and Radiobiology, Meibergdreef 9, Amsterdam, the Netherlands; Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, the Netherlands.

Translational oncology

|August 16, 2024

概括

HER2阳性食道腺癌显示免疫细胞透率降低和免疫疲劳标志物降低. 将VEGF与HER2一起向治疗可能会改善非响应者的治疗反应.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
胃肠病学胃肠病学

背景情况:

向HER2在食道腺癌 (EAC) 中表现有前途,但缺乏持久的反应.
瘤免疫微环境 (TIME) 显著影响治疗结果.
了解 HER2 阳性 EAC 中的 TIME 对于改善治疗策略至关重要.

研究的目的:

描述 HER2 阳性 EAC 的时间.
为了确定HER2-阳性和HER2-阴性瘤之间的TIME差异.
为了比较对抗HER2治疗的响应者与不响应者的TIME.

主要方法:

来自TRAP和接受新辅助化疗或放射治疗的对照队伍的83次活检的分析.
使用纳米链免疫瘤学面板 (750个基因) 进行向基因表达分析.
差异性基因表达分析比较HER2-阳性与HER2-阴性和响应者与非响应者组.

主要成果:

HER2表达与上皮细胞标记物 (EPCAM,E-cadherin) 相关联.
在HER2阳性瘤中,免疫细胞透率较低 (NK细胞,CD8T细胞) 和免疫衰竭标志物减少 (PDCD1LG2,CTLA4).
非响应者表现出免疫疲劳标记的基线表达增加,缺氧和VEGF信号传递.

结论:

HER2表达与上皮瘤特征有关.
HER2 阳性 TIME 已经减少了免疫透和降低了免疫衰竭信号,挑战了联合抗 HER2 和检查点抑制剂的合理性.
在非响应者中增加的VEGF信号表明了与VEGF和HER2向组合的潜在协同作用.

关键词:

血管新生的产生.食道癌是食道癌的一个类型.在HER2阳性瘤中.免疫系统疲免疫系统疲瘤的免疫微环境

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