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:Comprehensive characterization of tumor immune landscape following oncolytic virotherapy by single-cell RNA sequencing.
Comprehensive characterization of tumor immune landscape following oncolytic virotherapy by single-cell RNA sequencing.
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溶瘤病毒治疗改善癌症免疫治疗的一个重要机制是诱导肿瘤微环境(TME)中免疫格局发生显著变化。尽管有这一观点及其潜在的治疗意义,但由病毒治疗诱导的癌组织中免疫变化的全面分析尚未被阐明。
我们对经HSV-2基溶瘤病毒治疗的癌组织进行了单细胞RNA测序分析,以表征TME中的免疫原性变化。我们专门分析并比较了病毒治疗和未治疗肿瘤之间的免疫细胞组成。
我们还应用CellChat分析了浸润免疫细胞之间复杂的相互作用。我们的数据揭示,病毒治疗后,除其他重要免疫细胞(包括CD4+、CD8+和NK细胞)外,B细胞也显著浸润。
进一步分析确定了浸润免疫细胞的不同亚群组成及其在病毒治疗后的激活状态。CellChat分析所揭示的浸润免疫细胞之间密集的相互作用可能进一步塑造有利于产生抗肿瘤免疫的免疫格局。
我们的发现将有助于设计将免疫治疗纳入病毒治疗以进行临床转化的新策略。此外,B细胞的显著浸润使其适合将病毒治疗与免疫检查点抑制剂联合使用。
An important mechanism of oncolytic virotherapy in ameliorating cancer immunotherapy is by inducing significant changes in the immune landscape in the tumor microenvironment (TME). Despite this notion and the potential therapeutic implications, a comprehensive analysis of the immune changes in carcinomas induced by virotherapy has not yet been elucidated.
We conducted single-cell RNA sequencing analysis on carcinomas treated with an HSV-2-based oncolytic virus to characterize the immunogenic changes in the TME.
We specifically analyzed and compared the immune cell composition between viral treated and untreated tumors.
We also applied CellChat to analyze the complex interactions among the infiltrated immune cells.
Our data revealed significant infiltration of B cells in addition to other important immune cells, including CD4 + , CD8 + , and NK cells following virotherapy.
Further analysis identified distinct subset compositions of the infiltrated immune cells and their activation status upon virotherapy. The intensive interactions among the infiltrated immune cells as revealed by CellChat analysis may further shape the immune landscape in favor of generating antitumor immunity.
Our findings will facilitate the design of new strategies in incorporating immunotherapy into virotherapy for clinical translation.
Moreover, the significant infiltration of B cells makes it suitable for combining virotherapy with immune checkpoint inhibitors.
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