Tumor-derived exosomes antagonize innate antiviral immunity

Gao Liang; Wang Lin; Dai Tong; Jin Ke; Zhang Zhengkui; Wang Shuai; Xie Feng; Fang Pengfei; Yang Bing; Huang Huizhe; van Dam Hans; Zhou Fangfang; Zhang Long

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Tumor-derived exosomes antagonize innate antiviral immunity

机译：肿瘤衍生的外泌体拮抗天生的抗病毒免疫力

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Malignancies can compromise innate immunity, but the mechanisms of this are largely unknown. Here we found that, via tumor-derived exosomes (TEXs), cancers were able to transfer activated epidermal growth factor receptor ( EGFR) to host macrophages and thereby suppress innate antiviral immunity. Screening of the human kinome identified the kinase MEKK2 in macrophages as an effector of TEX-delivered EGFR that negatively regulated the antiviral immune response. In the context of experimental tumor implantation, MEKK2-deficient mice were more resistant to viral infection than were wild-type mice. Injection of TEXs into mice reduced innate immunity, increased viral load and increased morbidity in an EGFR- and MEKK2-dependent manner. MEKK2 phosphorylated IRF3, a transcription factor crucial for the production of type I interferons; this triggered poly-ubiquitination of IRF3 and blocked its dimerization, translocation to the nucleus and transcriptional activity after viral infection. These findings identify a mechanism by which cancer cells can dampen host innate immunity and potentially cause patients with cancer to become immunocompromised.

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来源
《Nature immunology》 |2018年第3期|共12页
作者
Gao Liang; Wang Lin; Dai Tong; Jin Ke; Zhang Zhengkui; Wang Shuai; Xie Feng; Fang Pengfei; Yang Bing; Huang Huizhe; van Dam Hans; Zhou Fangfang; Zhang Long;
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作者单位

Inst Life Sci Hangzhou Zhejiang Peoples R China;

Soochow Univ Inst Biol &

Med Sci Suzhou Peoples R China;

Inst Life Sci Hangzhou Zhejiang Peoples R China;

Inst Life Sci Hangzhou Zhejiang Peoples R China;

Inst Life Sci Hangzhou Zhejiang Peoples R China;

Soochow Univ Inst Biol &

Med Sci Suzhou Peoples R China;

Inst Life Sci Hangzhou Zhejiang Peoples R China;

Inst Life Sci Hangzhou Zhejiang Peoples R China;

Univ Calif San Francisco Dept Pharmaceut Chem San Francisco CA 94143 USA;

Chonqing Med Univ Fac Basic Med Sci Chongqing Peoples R China;

Leiden Univ Med Ctr Canc Genom Ctr Netherlands Dept Mol Cell Biol Leiden Netherlands;

Soochow Univ Inst Biol &

Med Sci Suzhou Peoples R China;

Inst Life Sci Hangzhou Zhejiang Peoples R China;

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正文语种 eng
中图分类医学免疫学;
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Tumor-derived exosomes antagonize innate antiviral immunity

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