通过调节CCR2和贩运,STYK1调解NK细胞的抗瘤反应
Junming He1,2, Yuexi He3, Ruojia Biao4,5,6,7
1Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, 102218, China.
氨酸/氨酸/氨酸激酶1 (STYK1) 对于自然杀手 (NK) 细胞的抗瘤活性至关重要. 删除STYK1会损害NK细胞的迁移,并促进瘤的生长,突出显示STYK1.
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:
- 氨酸/氨酸/氨酸激酶1 (STYK1),一种类似于受体蛋白-氨酸激酶 (RPTK) 的分子,涉及促进瘤发生和转移.
- 在自然杀手 (NK) 细胞中,STYK1的表达特别高,这表明它可能在免疫监测中发挥作用.
研究的目的:
- 研究STYK1在NK细胞中的功能及其在抗瘤免疫中的作用.
- 阐明STYK1在瘤微环境中影响NK细胞活性的机制.
主要方法:
- 使用CRISPR/Cas9技术生成了STYK1被删除的小鼠.
- 在无瘤和瘤条件下评估NK细胞数量,发育和功能.
- 利用了各种瘤模型 (B16F10黑色素瘤,MMTV-PyMT乳腺癌) 和NK细胞特异性点清除试验.
- 在STYK1缺乏和野生型NK细胞上进行RNA测序,以分析信号通路.
- 在缺乏STYK1的NK细胞中,量化化基因受体表达,特别是CCR2.
主要成果:
- 在没有瘤的小鼠中,STYK1的删除没有影响NK细胞的发育或功能.
- 令人惊的是,STYK1删除在多个模型中促进了瘤进展,与减少NK细胞透到瘤相关.
- 缺少STYK1的NK细胞显示出迁移和粘附信号受损,CCR2表达显著降低.
- 在质瘤患者中,STYK1表达与瘤进展相反相关.
结论:
- 在NK细胞中,STYK1的表达对于调解抗瘤反应至关重要.
- STYK1调节NK细胞向瘤组织的迁移,部分通过调节CCR2的表达.
- 致癌性STYK1通过增强NK细胞介导的瘤监测而起瘤抑制作用.
更多相关视频
06:55Measurement of Natural Killer Cell-Mediated Cytotoxicity and Migration in the Context of Hepatic Tumor Cells
Published on: February 22, 2020
05:24Two Flow Cytometric Approaches of NKG2D Ligand Surface Detection to Distinguish Stem Cells from Bulk Subpopulations in Acute Myeloid Leukemia
Published on: February 21, 2021
相关概念视频
Cytotoxic T Cells-mediated Immune Response
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Cells of the Innate Immune Response
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists
Immune Surveillance by NK Cells and Phagocytes
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
