The pan-cancer landscape of crosstalk between epithelial-mesenchymal transition and immune evasion relevant to prognosis and immunotherapy response.
The pan-cancer landscape of crosstalk between epithelial-mesenchymal transition and immune evasion relevant to prognosis and immunotherapy response.
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上皮间质转化和免疫逃避之间的串扰与预后和免疫治疗反应相关的泛癌景观
DOI：
10.1038/s41698-021-00200-4
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发表时间：
2021-06-22
影响因子：
7.9
通讯作者：
Zheng T
中科院分区：
文献类型：
--
作者：
Wang G;Xu D;Zhang Z;Li X;Shi J;Sun J;Liu HZ;Li X;Zhou M;Zheng T
一个新兴的证据体最近认识到上皮间质转化（EMT）和免疫反应的共存。然而，缺乏对EMT和免疫逃逸程序之间相互作用的系统水平的观点和调查，以及它们对各种类型癌症的肿瘤行为和临床结果的影响。在这里，我们进行了全面的多组学分析，以表征EMT和免疫逃避之间的串扰及其在17种实体癌中的临床相关性。我们的研究表明，泛癌共享的EMT和免疫逃避之间存在复杂和动态的免疫调节串扰，并且串扰与癌症预后和免疫治疗反应显著相关。基因组学和免疫基因组学的综合定量分析显示，免疫浸润的细胞组成、非同义突变负荷、染色体不稳定性和致癌基因改变与EMT和免疫逃避之间的平衡有关。最后，我们提出了一个评分模型，称为EMT-CYT指数（ECI）量化EMT免疫轴，这是一个上级预测预后和免疫治疗反应的不同恶性肿瘤。通过提供EMT和免疫逃避之间的串扰的系统概述，我们的研究强调了泛癌症EMT免疫串扰作为解剖癌症进展的分子机制和指导更有效和更广泛的免疫治疗策略的范例的潜力。
An emerging body of evidence has recently recognized the coexistence of epithelial-mesenchymal transition (EMT) and immune response. However, a systems-level view and survey of the interplay between EMT and immune escape program, and their impact on tumor behavior and clinical outcome across various types of cancer is lacking. Here, we performed comprehensive multi-omics analyses to characterize the landscape of crosstalk between EMT and immune evasion and their clinical relevance across 17 types of solid cancer. Our study showed the presence of complex and dynamic immunomodulatory crosstalk between EMT and immune evasion shared by pan-cancer, and the crosstalk was significantly associated with cancer prognosis and immunotherapy response. Integrative quantitative analyses of genomics and immunogenomics revealed that cellular composition of immune infiltrates, non-synonymous mutation burden, chromosomal instability and oncogenic gene alterations are associated with the balance between EMT and immune evasion. Finally, we proposed a scoring model termed EMT-CYT Index (ECI) to quantify the EMT-immunity axis, which was a superior predictor of prognosis and immunotherapy response across different malignancies. By providing a systematic overview of crosstalk between EMT and immune evasion, our study highlights the potential of pan-cancer EMT-immunity crosstalk as a paradigm for dissecting molecular mechanisms underlying cancer progression and guiding more effective and generalized immunotherapy strategies.
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影响因子：
64.8
作者：
通讯作者：
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影响因子：
3.8
作者：
Haslehurst AM;Koti M;Dharsee M;Nuin P;Evans K;Geraci J;Childs T;Chen J;Li J;Weberpals J;Davey S;Squire J;Park PC;Feilotter H
通讯作者：
Feilotter H
影响因子：
10.3
作者：
Cortez, Maria Angelica;Ivan, Cristina;Welsh, James W.
通讯作者：
Welsh, James W.
影响因子：
4.4
作者：
Bulzico, Daniel;Torres, Davi Coe;Vieira Neto, Leonardo
通讯作者：
Vieira Neto, Leonardo
影响因子：
5.4
作者：
Kmieciak, Maciej;Knutson, Keith L.;Manjili, Masoud H.
通讯作者：
Manjili, Masoud H.