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:Noninvasively Real-Time Monitoring In-Vivo Immune Cell and Tumor Cell Interaction by NIR-II Nanosensor.
Noninvasively Real-Time Monitoring In-Vivo Immune Cell and Tumor Cell Interaction by NIR-II Nanosensor.
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免疫细胞治疗作为一种新型癌症治疗方法具有巨大前景,但其疗效常因响应延迟而受限,基于当前诊断方法需要每2-3周进行一次评估。对免疫细胞-肿瘤细胞相互作用的早期评估可提供更及时的治疗效果信息,从而调整治疗方案。
本研究报道了一种非侵入性纳米传感器(C8R-DSNP),用于在第二近红外长波长(NIR-II-L)窗口(1500-1900 nm)实时监测体内免疫细胞活动,该窗口具有深层组织透明性。C8R-DSNP对caspase-8快速响应,caspase-8是自然杀伤(NK-92)细胞与肿瘤细胞相互作用过程中产生的关键凋亡信号分子。利用比率型NIR-II-L荧光成像,捕获了小鼠模型中NK-92细胞与肿瘤细胞相互作用的体内动态观察结果。这些结果表明,肿瘤细胞凋亡最早在NK-92细胞输注后4.5 h即发生。
此外,体外尿液成像通过切割的荧光小分子证实了凋亡的启动,而血管和肿瘤内的单细胞追踪进一步阐明了免疫细胞动态。这种实时NIR-II-L监测方法为优化免疫细胞治疗策略提供了有价值的见解。
Immunocytotherapy holds significant promise as a novel cancer treatment, but its effectiveness is often hindered by delayed responses, requiring evaluations every 2-3 weeks based on current diagnostic methods. Early assessment of immune cell-tumor cell interactions could provide more timely insights into therapeutic efficacy, enabling adjustments to treatment plans. In this study, a noninvasive nanosensor (C8R-DSNP) for real-time monitoring of in vivo immune cell activities in the second near-infrared long-wavelength (NIR-II-L) window (1500-1900 nm), which offers deep tissue transparency, is reported.
The C8R-DSNP responds rapidly to caspase-8, a key apoptotic signaling molecule generated during interactions between natural killer (NK-92) cells and tumor cells. Using ratiometric NIR-II-L fluorescence imaging, dynamic in vivo observations of NK-92 cells' engagement with tumor cells in a mouse model are captured. These results demonstrate tumor cells apoptosis that happens as early as 4. 5 h after NK-92 cells infusion.
Additionally, in vitro urine imaging confirmed the initiation of apoptosis via cleaved fluorescent small molecules, while single-cell tracking within blood vessels and tumors further elucidated immune cell dynamics. This real-time NIR-II-L monitoring approach offers valuable insights for optimizing immunocytotherapy strategies.
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