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单细胞分析揭示了肝细胞癌中与PD-1阻断反应相关的免疫特征

Yao Li¹, Fengwei Li¹, Lei Xu²

¹Department of Hepatic Surgery II, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China.

|July 1, 2024

概括

肝细胞癌 (HCC) 的免疫疗法耐药性与特定的免疫细胞有关. 用抗Csf1r抗体向TREM2+巨细胞可以改善HCC患者的抗PD-1治疗反应.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
基因组学就是基因组学.

背景情况:

免疫疗法对肝细胞癌 (HCC) 是有前途的,但患者的反应是可变的.
了解响应者与不响应者的瘤微环境 (TME) 对于克服免疫疗法耐药性至关重要.

研究的目的:

为了比较分析响应和不响应抗PD-1治疗的HCC患者的TME.
确定免疫疗法耐药性的机制和HCC.中的潜在治疗点.

主要方法:

单细胞和空间转录基因组测序 (10x基因组学) 的HCC患者样本 (响应者和非响应者).
使用像Harmony这样的算法进行数据整合,并通过免疫光学,流细胞计和体内实验进行验证.
对未经治疗,反应和不反应的HCC患者的公共单细胞数据集的分析.

主要成果:

"免疫屏障"有助于免疫疗法的有效性受到限制,其特点是不响应者中TREM2+巨细胞的增加.
抗Csf1r单克隆抗体减少了这些免疫抑制性巨细胞,增强了抗PD-1治疗效果.
确定了具有瘤杀伤潜力的TCR+巨细胞,IL1B+cDC2作为一个关键的cDC2亚型,以及缺少THEMIShi CD8+ T细胞,可能会降低免疫治疗效果. 在治疗后,CD8+ T细胞表现出压力,疲劳和衰老的迹象.

结论:

独特的免疫TME概况区分了响应性,不响应性和未经治疗的HCC患者,解释了可变的免疫疗法疗效.
确定的特定细胞和分子具有独特的能力,可以向改善HCC的免疫治疗结果.

关键词:

在PD-1中使用PD-1.肝细胞癌是肝细胞癌.免疫微观环境免疫微环境免疫疗法免疫疗法一个单细胞的单细胞.

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