CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
过度活跃的 Rac 刺激对活靶细胞的同类相食并增强 CAR-M 介导的癌细胞杀伤
英文原题：Hyperactive Rac stimulates cannibalism of living target cells and enhances CAR-M-mediated cancer cell killing.
查看英文原题
Hyperactive Rac stimulates cannibalism of living target cells and enhances CAR-M-mediated cancer cell killing.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
中文摘要
21kD GTPase Rac 是一种进化上古老的细胞形状和行为调节因子。Rac2 主要表达于造血细胞中，对细胞的存活和运动至关重要。过度激活突变 Rac2 E62K 也会导致人类免疫缺陷，但其机制仍不清楚。
在此，我们报道在果蝇中，过度激活的 Rac 刺激卵巢细胞吞噬邻近细胞，破坏组织。随后我们证明，过度激活的 Rac2 E62K 刺激人 HL60 来源的巨噬细胞样细胞吞噬并杀死活的 T 细胞白血病细胞。原代小鼠 Rac2 +/E62K 骨髓来源巨噬细胞也因巨噬细胞过度活跃与 T 细胞对吞噬超敏的联合作用而吞噬原代 Rac2 +/E62K T 细胞。
此外，Rac2 +/E62K 巨噬细胞以非自主方式刺激野生型巨噬细胞吞噬 T 细胞。Rac2 E62K 还以 CAR 依赖的方式增强表达嵌合抗原受体巨噬细胞（CAR-M）对靶癌细胞的吞噬。
我们提出，Rac 介导的细胞吞噬可能促进 Rac2 +/E62K 人类免疫缺陷并增强 CAR-M 癌症免疫治疗。
展开英文摘要原文
The 21kD GTPase Rac is an evolutionarily ancient regulator of cell shape and behavior. Rac2 is predominantly expressed in hematopoietic cells where it is essential for survival and motility. The hyperactivating mutation Rac2 E62K also causes human immunodeficiency, although the mechanism remains unexplained.
Here, we report that in Drosophila, hyperactivating Rac stimulates ovarian cells to cannibalize neighboring cells, destroying the tissue.
We then show that hyperactive Rac2 E62K stimulates human HL60-derived macrophage-like cells to engulf and kill living T cell leukemia cells. Primary mouse Rac2 +/E62K bone-marrow-derived macrophages also cannibalize primary Rac2 +/E62K T cells due to a combination of macrophage hyperactivity and T cell hypersensitivity to engulfment.
Additionally, Rac2 +/E62K macrophages non-autonomously stimulate wild-type macrophages to engulf T cells. Rac2 E62K also enhances engulfment of target cancer cells by chimeric antigen receptor-expressing macrophages (CAR-M) in a CAR-dependent manner.
We propose that Rac-mediated cell cannibalism may contribute to Rac2 +/E62K human immunodeficiency and enhance CAR-M cancer immunotherapy.
论文信息
- 作者
- Mishra AK、Rodriguez M、Torres AY、Smith M、Rodriguez A、Bond A、Morrissey MA、Montell DJ
- 单位
- Molecular Cellular and Developmental Biology Department, University of California, Santa Barbara, CA 93106.United States
- 文献类型
- 美国 NIH 资助研究 · 非美国政府资助研究
- 期刊
- Proceedings of the National Academy of Sciences of the United States of America2023 Dec 26
- 原文标识
- PubMed 38109551 · DOI 10.1073/pnas.2310221120
在 PubMed 查看 → 出版商原文（DOI） 全文 PDF（PMC）· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →