RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Smartly Assembled near-Micron RF-Responsive Agents Bridge Transarterial Embolization and Immunothermal Potentiation.
Smartly Assembled near-Micron RF-Responsive Agents Bridge Transarterial Embolization and Immunothermal Potentiation.
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肝细胞癌(HCC)仍然是一个重大的临床挑战,因为手术、射频消融(RFA)和经动脉栓塞(TAE)等传统疗法的疗效有限。在此,我们开发了一种创新的TAE与免疫热疗策略,基于智能组装的近微米级层状双氢氧化物颗粒,共载STING激动剂(NM-LDHs-cGP)。通过对局部电荷波动和微环境变化的智能响应,NM-LDHs发生自组装和分级堆叠,形成稳定的血管栓塞剂,从而实现优异的栓塞效果和对射频诱导热刺激的出色响应性。NM-LDHs-cGP激活cGAS-STING通路,促进树突状细胞成熟,并引发强效的CD8 + T和NK细胞应答。使用人HCC组织和免疫细胞的转化研究证实了其增强RFA诱导的细胞毒性并触发强效先天性和适应性免疫激活的能力。这些发现确立了智能组装的NM-LDHs-cGP作为肝癌联合栓塞-热消融-免疫治疗的一种有前景的范式。
Hepatocellular carcinoma (HCC) remains a significant clinical challenge due to the limited efficacy of conventional treatments like surgery, radiofrequency ablation (RFA), and transarterial embolization (TAE).
Here, we develop an innovative TAE and immunothermal therapy strategy based on smartly assembled near-micron layered double hydroxide particles co-loaded with STING agonist (NM-LDHs-cGP). By smartly responding to local charge fluctuations and microenvironmental changes, NM-LDHs undergo self-assembly and hierarchical stacking to form stable vascular embolic agents, thereby achieving superior embolization efficacy and excellent responsiveness to radiofrequency-induced thermal stimulation.
NM-LDHs-cGP activates the cGAS-STING pathway, promotes dendritic cell maturation, and elicits robust CD8 + T and NK cell responses. Translational studies using human HCC tissues and immune cells confirm its ability to enhance RFA-induced cytotoxicity and trigger potent innate and adaptive immune activation.
These findings establish smartly assembled NM-LDHs-cGP as a promising paradigm for combinatorial embolization-thermal ablation-immunotherapy in liver cancer.
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