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多组学分析揭示肝内胆管癌免疫浸润的复杂性和动态变化

Multi-Omics Profiling Unveils the Complexity and Dynamics of Immune Infiltrates in Intrahepatic Cholangiocarcinoma.

作者信息

Li Xuan, Wang Yan, Guan Renchu, Sheng Nan, Zhang Shuangquan

机构信息

Key Laboratory of Symbolic Computation and Knowledge Engineering of Ministry of Education, College of Computer Science and Technology, Jilin University, Changchun 130012, China.

School of Cyber Science and Engineering, Nanjing University of Science and Technology, Nanjing 210094, China.

出版信息

Biology (Basel). 2024 Oct 11;13(10):816. doi: 10.3390/biology13100816.

DOI:10.3390/biology13100816
PMID:39452125
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11504529/
Abstract

Intrahepatic cholangiocarcinoma (ICC) is a highly heterogeneous malignancy. The reasons behind the global rise in the incidence of ICC remain unclear, and there exists limited knowledge regarding the immune cells within the tumor microenvironment (TME). In this study, a more comprehensive analysis of multi-omics data was performed using machine learning methods. The study found that the immunoactivity of B cells, macrophages, and T cells in the infiltrating immune cells of ICC exhibits a significantly higher level of immunoactivity in comparison to other immune cells. During the immune sensing and response, the effect of antigen-presenting cells (APCs) such as B cells and macrophages on activating NK cells was weakened, while the effect of activating T cells became stronger. Simultaneously, four distinct subpopulations, namely BLp, MacrophagesLp, BHn, and THn, have been identified from the infiltrating immune cells, and their corresponding immune-related marker genes have been identified. The immune sensing and response model of ICC has been revised and constructed based on our current comprehension. This study not only helps to deepen the understanding the heterogeneity of infiltrating immune cells in ICC, but also may provide valuable insights into the diagnosis, evaluation, treatment, and prognosis of ICC.

摘要

肝内胆管癌(ICC)是一种高度异质性的恶性肿瘤。ICC全球发病率上升背后的原因尚不清楚,并且关于肿瘤微环境(TME)中的免疫细胞的了解有限。在本研究中,使用机器学习方法对多组学数据进行了更全面的分析。研究发现,与其他免疫细胞相比,ICC浸润性免疫细胞中的B细胞、巨噬细胞和T细胞的免疫活性表现出显著更高的水平。在免疫感应和反应过程中,B细胞和巨噬细胞等抗原呈递细胞(APC)激活NK细胞的作用减弱,而激活T细胞的作用增强。同时,已从浸润性免疫细胞中鉴定出四个不同的亚群,即BLp、巨噬细胞Lp、BHn和THn,并确定了它们相应的免疫相关标记基因。基于我们目前的理解,对ICC的免疫感应和反应模型进行了修订和构建。本研究不仅有助于加深对ICC浸润性免疫细胞异质性的理解,还可能为ICC的诊断、评估、治疗和预后提供有价值的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b440/11504529/91368d1101c7/biology-13-00816-g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b440/11504529/9b09021ff93c/biology-13-00816-g003.jpg
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