细胞间CRISPR查揭示了癌细胞细胞的调节剂
Roarke A Kamber1, Yoko Nishiga1,2,3, Bhek Morton1
1Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
Nature
|September 9, 2021
概括
研究人员发现脂肪细胞等离子膜相关蛋白 (APMAP) 是癌细胞逃避巨细胞灭菌的关键因素. 失去APMAP可以通过免疫疗法增强癌细胞的消除,从而提供新的治疗策略.
科学领域:
- 免疫学
- 癌症生物学
- 遗传学
背景情况:
- 单克隆抗体疗法通过刺激巨细胞消化来消除癌细胞.
- 癌细胞有不完全理解的机制来逃避细胞分裂,限制治疗效果.
研究的目的:
- 确定调节癌细胞易受抗体依赖细胞化 (ADCP) 的新型因素.
- 通过巨细胞介导的癌细胞抵抗机制的发现.
主要方法:
- 在癌细胞和巨细胞中开发一个无偏的全基因组CRISPR淘汰和过度表达查平台.
- 使用补充选方法识别ADCP监管机构.
主要成果:
- 在癌细胞中,脂肪细胞等离子膜相关蛋白 (APMAP) 被确定为ADCP的新型调节剂.
- 当与瘤抗原向或CD47阻断抗体相结合时,APMAP的损失显著增强了各种癌细胞的细胞形成.
- 与瘤向单克隆抗体协同作用的APMAP损失在体内抑制瘤生长.
- 发现G蛋白结合受体GPR84通过巨细胞促进了APMAP缺乏的癌细胞的细胞增强.
结论:
- APMAP是一种癌症内在因子,促进抗体驱动的细胞形成的抵抗力.
- 向APMAP是一种有前途的策略,可以克服癌细胞逃避并提高免疫疗法的有效性.
- 这项研究扩大了对巨细胞消化调节和癌症免疫逃避机制的理解.
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