In Vivo Epigenetic CRISPR Screen Identifies Asf1a as an Immunotherapeutic Target in Kras-Mutant Lung Adenocarcinoma

体内表观遗传 CRISPR 筛选确定 Asf1a 是 Kras 突变肺腺癌的免疫治疗靶点

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作者:Fei Li, Qingyuan Huang, Troy A Luster, Hai Hu, Hua Zhang, Wai-Lung Ng, Alireza Khodadadi-Jamayran, Wei Wang, Ting Chen, Jiehui Deng, Michela Ranieri, Zhaoyuan Fang, Val Pyon, Catríona M Dowling, Ece Bagdatlioglu, Christina Almonte, Kristen Labbe, Heather Silver, Alexandra R Rabin, Kandarp Jani, Aris

Significance

Using an in vivo epigenetic CRISPR screen, we identified Asf1a as a critical regulator of LUAD sensitivity to anti-PD-1 therapy. Asf1a deficiency synergized with anti-PD-1 immunotherapy by promoting M1-like macrophage polarization and T-cell activation. Thus, we provide a new immunotherapeutic strategy for this subtype of patients with LUAD.See related commentary by Menzel and Black, p. 179.This article is highlighted in the In This Issue feature, p. 161.

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