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在乙型肝炎病毒 (HBV) 与肝细胞癌 (HCC) 相关的两种不同的免疫亚型的识别

Davide De Battista¹, Rylee Yakymi¹, Evangeline Scheibe¹

¹Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

|April 13, 2024

概括

由乙型肝炎病毒 (HBV) 驱动的肝细胞癌 (HCC) 显示了两个不同的免疫亚型. 识别这些免疫特征可以帮助预测患者对免疫疗法治疗的反应.

科学领域:

肝病学肝病学是一种肝病学.
免疫学免疫学免疫学
在瘤学瘤学.

背景情况:

肝细胞癌 (HCC) 经常与乙型肝炎病毒 (HBV) 感染有关,这代表了全球健康的重大挑战.
在HBV-HCC中的瘤微环境 (TME) 在免疫治疗反应中起着至关重要的作用,但仍然不完全理解.
了解TME异质性对于优化HBV-HCC的免疫检查点抑制剂疗法至关重要.

研究的目的:

描述HBV-HCC瘤微环境 (TME) 并识别不同的免疫亚型.
为了将TME特征与免疫治疗的潜在反应相关联,特别是检查点抑制剂.
研究不同免疫亚型中特定基因突变 (例如CTNNB1) 的作用.

主要方法:

分析了12名白种患者的肝样本,这些患者患有HBV相关的HCC.
广泛的免疫组织化学 (IHC) 用于免疫细胞透和 stromal 激活.
对结合的瘤和非瘤性肝脏组织进行转录形状分析.
整体外基因组测序 (WES) 用于识别遗传突变.

主要成果:

确定了两种不同的HBV-HCC亚型:"免疫性高"和"免疫性低".
免疫性高的亚型:特征是B细胞和T细胞透增加, stromal激活,抑制抗原呈现,高CTLA-4,低PD-1表达.
免疫性较低的亚型:显示淋巴细胞透和 stromal 激活的减少,CTNNB1 突变的患病率较高 (4/6 个案例) 与免疫性较高的亚型 (1/6 个案例) 相比.

结论:

在HBV相关的HCC中存在不同的免疫亚型,独立于周围的非瘤肝脏微环境.
这些亚型为HBV-HCC病原和免疫逃避机制提供了新的见解.
这些发现可能有助于选择可能受益于免疫治疗的患者,包括检查点抑制剂.

关键词:

在HCC中使用CTLA-4表达式.通过RNA测序进行RNA测序.乙型肝炎病毒的感染.肝细胞癌是肝细胞癌.在HCC中使用免疫检查点.瘤微环境是一个微环境.

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