通过抗塞尔B9疗法直接杀死瘤和免疫疗法
Liwei Jiang1, Yi-Jun Wang1, Jing Zhao1
1Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Cell
|November 26, 2020
概括
抑制血清蛋白酶抑制剂SerpinB9 (Sb9) 直接杀死癌细胞并增强抗瘤免疫力. 结合瘤和宿主中的Sb9缺乏,可以最大限度地控制癌症的生长和生存.
科学领域:
- 癌症学
- 免疫学
- 分子生物学
背景情况:
- 癌症治疗的目的是直接或通过免疫反应消除瘤,结合的方法显示出不同的成功.
- 血清蛋白酶抑制剂SerpinB9 (Sb9) 在瘤微环境 (TME) 中起到瘤细胞生存和免疫调节的作用.
研究的目的:
- 研究SerpinB9 (Sb9) 基因切除对控制癌症生长的治疗潜力.
- 探索Sb9缺乏对直接瘤杀死和宿主抗瘤免疫的综合作用.
主要方法:
- 在小鼠癌症模型中对SerpinB9 (Sb9) 进行基因切除.
- 评估TME内的瘤细胞死亡,T细胞介导免疫和免疫抑制细胞群.
- 评估瘤生长,存活率和Sb9抑制的治疗效果.
主要成果:
- Sb9 缺乏导致了依赖格兰酶B (GrB) 的瘤细胞死亡.
- 缺乏Sb9的小鼠表现出基于T细胞的增强抗瘤免疫力.
- 在Sb9缺乏的小鼠的TME中观察到GrB表达免疫抑制细胞的下降.
- 当瘤和宿主都缺乏Sb9时,可以达到最大的瘤生长控制和生存率的提高.
结论:
- 通过将直接杀死瘤与增强抗瘤免疫力相结合,针对SerpinB9 (Sb9) 提供了一种新的癌症治疗策略.
- 抑制Sb9是干扰TME并增强免疫疗法的有希望的方法.
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