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激活抗瘤免疫力并使检查点封锁

Wanqiang Sheng¹, Martin W LaFleur², Thao H Nguyen³

¹Division of Newborn Medicine and Epigenetics Program, Boston Children's Hospital, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.

|June 26, 2018

概括

通过增加重复元素表达和激活干扰素,抑制癌细胞中的LSD1增强了抗瘤免疫力. 这种方法增强了免疫疗法反应,

科学领域:

癌症生物学
免疫学
表观遗传学

背景情况:

染色体调节剂对基因表达至关重要,它们的失调会导致癌症.
激素脱甲基酶LSD1 (氨酸特异性脱甲基酶1) 涉及到各种癌症.

研究的目的:

研究LSD1在调节基因表达和抗瘤免疫力的作用.
探索LSD1抑制作为一种潜在的癌症治疗策略.

主要方法:

在癌细胞中切除LSD1.
对重复元素和RNA诱导沉默复合体 (RISC) 组件表达的分析.
对双链RNA (dsRNA) 应激和1型干扰素激活的评估.
在小鼠模型中评估瘤免疫性,T细胞透和对抗PD-1治疗的反应.
对TCGA数据进行分析,以确定LSD1表达与CD8+T细胞透之间的相关性.

主要成果:

消去LSD1增加了重复元素和内源逆转录病毒元素 (ERV) 的表达.
减少RISC组件的表达导致了dsRNA应激和1型干扰素激活.
减少LSD1增强了瘤免疫性和T细胞透,改善了抗PD-1疗法的反应.
在人类癌症中,TCGA数据显示LSD1表达和CD8+T细胞透之间存在反向相关性.

结论:

抑制LSD1增强了抗瘤免疫力,并提高了对免疫治疗的反应能力.
它是抗瘤免疫的关键抑制剂.
将LSD1抑制与PD- L) 1阻断结合在一起,是一个有前途的新型癌症治疗策略.

关键词:

一个LSD 一个MHC-1 PD-1/PD-L1 其他在RISC 透T细胞抗瘤免疫力 dsRNA 的时间内生逆转录病毒元素免疫检查点封锁干扰素

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