通过等级纳米诱导器促进内源性危险信号的积累,以扩大STING通路激活-中介瘤免疫疗法
Xiao-Kang Jin1, Shi-Man Zhang1, Zi-Han Xu1
1Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan 430072, P. R. China.
一种新型纳米诱导剂激活了干扰素基因 (cGAS-STING) 循环GMP-AMP合成酶刺激器通路,通过诱导瘤细胞中的热和内源性危险信号 (EDS),增强癌症免疫疗法并抑制瘤生长.
科学领域:
- 生物医学工程 生物医学工程
- 纳米技术纳米技术
- 免疫治疗是一种免疫疗法.
背景情况:
- 外源性干扰素基因刺激剂 (STING) 激动剂在体内使用时具有临床限制.
- 通过内源危险信号 (EDS) 激活cGAS-STING通路是一个有希望的替代方案.
- 细胞内EDS水平对于有效的cGAS-STING通路激活至关重要.
研究的目的:
- 开发一个pH响应的等级纳米诱导器 (FGMC),用于激活cGAS-STING通路.
- 调查FGMC诱导灭和EDS在瘤细胞中的积累的能力.
- 评估FGMC在增强癌症免疫疗法的潜力.
主要方法:
- 通过在MK571-Co2+ (MC) 协调中封装费里-葡萄糖氧化酶/MK571 (FGM) 来制造FGMC.
- 利用FGMC的酶活性来破坏瘤细胞平衡,并诱导热.
- 评估FGMC对细胞内dDNA和循环GMP-AMP水平以及cGAS-STING通路激活的影响.
主要成果:
- FGMC成功诱导了热和线粒体损伤,导致线粒体DNA释放.
- 通过抑制葡萄糖/NSUN2/TREX2轴和ABCC1载体,FGMC增强了细胞内dDNA和循环GMP-AMP积累.
- 激活瘤细胞和树突细胞中的cGAS-STING通路,从而产生强大的抗瘤免疫力.
结论:
- 通过诱导热和EDS的积累,FGMC有效地激活了cGAS-STING通路.
- 在癌症免疫治疗中,FGMC显示出作为常规STING激动剂的替代品的潜力.
- 纳米诱导剂通过唤起强烈的免疫反应来抑制瘤生长和转移.
更多相关视频
08:02In Vivo Immunogenicity Screening of Tumor-Derived Extracellular Vesicles by Flow Cytometry of Splenic T Cells
Published on: September 23, 2021
07:44Studying the Effects of Tumor-Secreted Paracrine Ligands on Macrophage Activation using Co-Culture with Permeable Membrane Supports
Published on: November 28, 2019
相关概念视频
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
The Tumor Microenvironment
Tumor Immunotherapy
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Amplifying Signals via Enzymatic Cascade
Autocrine Signaling
Autocrine Signaling in Macrophages
Under normal physiological conditions, autocrine signaling is essential for maintaining homeostasis. This process is well characterized in...
