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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >B regulatory cells and the tumor-promoting actions of TNF-α during squamous carcinogenesis
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B regulatory cells and the tumor-promoting actions of TNF-α during squamous carcinogenesis

机译：鳞癌发生过程中B调节细胞与TNF-α的促肿瘤作用

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摘要

The inflammatory cytokine TNF-α has been recognized as a critical tumor promoter, but the effector cells that mediate its action have not been fully characterized. Because B cells regulate squamous and prostate carcinogenesis, and Tnf~(-/-) mice harbor B-cell defects, we investigated the hypothesis that B cells are important effector cells for TNF-α-mediated promotion of cancer development. Using an adoptive transfer strategy and the 7,12-dimethylbenzla]anthra-cene/terephthalic acid (DMBA/TPA) two-stage model of skin carcinogenesis, we found that both B cells and TNF-α are critical for the development of DMBA/TPA-induced papilloma. Transfer of B cells from DMBA/TPA-treated wild-type mice to Tnf~(-/-) mice rescued papilloma development to a wild-type level, a result not observed when B cells from Tnf~(-/-) mice were transferred to Rag2~(-/-) mice or when TNF-α was eliminated selectively in B cells. Resistance to papilloma development in Tnf~(-/-) mice was associated with increased IFN-γ and CD8~+ T cells in skin and a significant reduction in IL-10-producing B regulatory cells alongside an increase in IFN-γ-producing CD8~+ T cells in the spleen. These data indicate that during DMBA/TPA-induced squamous carcinogenesis TNF-α mediates tumor-promoting activity via regulatory B cells that repress antitumor immunity.
机译：炎性细胞因子TNF-α已被认为是关键的肿瘤启动子，但尚未完全表征介导其作用的效应细胞。因为B细胞调节鳞状和前列腺癌变，并且Tnf〜（-/-）小鼠具有B细胞缺陷，所以我们研究了B细胞是TNF-α介导的癌症发展的重要效应细胞的假说。使用过继转移策略和7,12-二甲基苯并/对苯二甲酸（DMBA / TPA）皮肤癌变的两个阶段模型，我们发现B细胞和TNF-α对DMBA / TPA诱发的乳头状瘤。 DMBA / TPA处理的野生型小鼠的B细胞向Tnf〜（-/-）小鼠的转移将乳头状瘤的发展挽救到了野生型水平，而当Tnf〜（-/-）小鼠的B细胞在转移至Rag2〜（-/-）小鼠或在B细胞中选择性消除TNF-α时。 Tnf〜（-/-）小鼠对乳头瘤发展的抵抗力与皮肤中的IFN-γ和CD8〜+ T细胞增加以及IL-10产生的B调节细胞显着减少以及IFN-γ产生的增加有关脾脏中的CD8〜+ T细胞。这些数据表明，在DMBA / TPA诱导的鳞状癌变过程中，TNF-α通过抑制抗肿瘤免疫力的调节性B细胞介导肿瘤促进活性。

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    Tiziana Schioppa; Robert Moore; Richard G. Thompson; Elizabeth C. Rosser; Hagen Kulbe; Sergei Nedospasov; Claudia Mauri; Lisa M. Coussens; Frances R. Balkwill;

  • 作者单位

    Centre for Cancer and Inflammation, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, United Kingdom;

    Centre for Cancer and Inflammation, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, United Kingdom;

    Centre for Cancer and Inflammation, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, United Kingdom;

    Centre for Rheumatology Research, Department of Medicine, University College London, London W1 4JF, United Kingdom;

    Centre for Cancer and Inflammation, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, United Kingdom;

    Engelhardt Institute of Molecular Biology, Moscow 119991, Russia,German Rheumatism Research Center, a Leibniz Institute, D-13553 Berlin, Germany;

    Centre for Rheumatology Research, Department of Medicine, University College London, London W1 4JF, United Kingdom;

    Department of Pathology Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143,Department of Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143;

    Centre for Cancer and Inflammation, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, United Kingdom;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    immune cells; inflammation; tumor microenvironment;

    机译：免疫细胞炎;肿瘤微环境;

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