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:Differential Effector Function of Tissue-Specific Natural Killer Cells against Lung Tumors.
Differential Effector Function of Tissue-Specific Natural Killer Cells against Lung Tumors.
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这些发现强调了来自不同组织的 NK 细胞在暴露于 LL/2 肿瘤细胞之前就具有不同的效应能力。这凸显了组织特异性 NK 细胞异质性的重要性及其对抗肿瘤细胞毒性的影响。认识到这些不同的组织特异性受体表达模式将有助于开发更有效的基于 NK 细胞的癌症治疗方法。
自然杀伤(NK)细胞是先天淋巴样细胞,能够直接杀伤靶细胞,同时调节免疫效应应答。尽管具有多功能能力,但对其可塑性和异质性的了解有限,阻碍了开发有效的基于NK细胞的癌症疗法的进展。在本研究中,我们探讨了NK细胞的组织异质性及其与针对肺部肿瘤的表型和效应功能的关系。
使用悬滴肿瘤球和皮下建立的LL/2 (LLC1) 肺部肿瘤模型,我们通过多参数流式细胞术、荧光成像和细胞毒性试验,检查了NK细胞受体多样性及其与组织特异性细胞毒性的相关性。
我们发现了组织特异性NK细胞上细胞表面受体表达的独特模式,这些模式对抗肿瘤活性至关重要。线性回归数学分析进一步揭示,在肝脏和骨髓等组织的NK细胞中,活化相关细胞表面受体与细胞毒性能力之间存在显著正相关。
Using hanging drop tumor spheroid and subcutaneously established LL/2 (LLC1) lung tumor models, we examined NK cell receptor diversity and its correlation with tissue-specific cytotoxicity through multiparametric flow cytometry, fluorescence imaging, and cytotoxicity assays.
We identified distinct patterns of cell surface receptors expression on tissue-specific NK cells that are crucial for antitumor activity. Linear regression mathematical analyses further revealed significant positive correlations between activation-associated cell surface receptors and cytotoxic capacity in NK cells from tissues such as the liver and bone marrow.
These findings underscore the differential effector capacities of NK cells from distinct tissues, even prior to exposure to LL/2 tumor cells. This highlights the significance of tissue-specific NK cell heterogeneity and its impact on their antitumor cytotoxicity. Recognizing these distinct tissue-specific receptor expression patterns will be instrumental in developing more efficacious NK cell-based cancer treatments.
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