通过产生淘汰赛小鼠来研究TIGIT对瘤的活性
Ahmed Rishiq1, Reem Bsoul2, Ophir Pick1
1The Concern Foundation Laboratories at the Lautenberg Center for Immunology and Cancer Research, Institute for Medical Research Israel Canada (IMRIC), Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Oncoimmunology
|June 1, 2023
概括
鼠标TIGIT是一种抑制受体,只与PVR相互作用. 消除TIGIT可以增强天然杀手细胞对瘤的活性,在体内减缓癌症的进展,并改善瘤细胞的杀死.
科学领域:
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
- 分子生物学分子生物学
背景情况:
- 免疫检查点疗法 (抗PD1,CTLA4) 已经改变了癌症治疗.
- 许多患者对当前的免疫疗法没有反应,需要新的治疗点.
- TIGIT是免疫细胞上的抑制受体,但其在小鼠中的功能和连接物尚未完全理解.
研究的目的:
- 为了研究小鼠TIGIT的连接体和体内功能.
- 为了确定小鼠TIGIT是否与人类TIGIT相同的配体相互作用.
- 评估TIGIT缺陷对抗瘤免疫力的影响.
主要方法:
- 通过CRISPR-Cas9基因编辑生成缺TIGIT的小鼠.
- 自然杀手 (NK) 细胞细胞毒性和脱粒的评估.
- 在体内瘤进展研究比较野生型 (WT) 和TIGIT淘汰赛 (KO) 小鼠.
主要成果:
- 发现小鼠的TIGIT与小鼠PVR (mPVR) 完全相互作用.
- 与TIGIT KO小鼠相比,在WT小鼠中NK细胞细胞毒性和脱粒降低.
- 在TIGIT KO小鼠中,瘤的进展明显较WT小鼠慢.
结论:
- 鼠标TIGIT只有一个连接体,PVR.
- 缺少TIGIT可以增强NK细胞介导的抗瘤反应.
- 准TIGIT可能是改善癌症免疫疗法的有希望的策略.
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