Tumor-educated tolerogenic dendritic cells induce CD3epsilon down-regulation and apoptosis of T cells through oxygen-dependent pathways

The Journal of Immunology : Official Journal of the American Association of Immunologists
Dong-Ming KuangLimin Zheng

Abstract

Defects in the CD3/TCR complex and impairment of T cell function are necessary for tumor evasion, but the underlying mechanisms are incompletely understood. We found that culture supernatants from several types of solid tumor cell lines drove human monocytes to become tolerogenic semimature dendritic cells (TDCs). Upon encountering T cells, the TDCs triggered rapid down-regulation of CD3epsilon and TCR-alpha/beta and subsequent apoptosis in autologous T cells. Consistent with these results, accumulation of immunosuppressive DCs coincided with CD3epsilon down-regulation and T cell deletion in cancer nests of human tumors. The impaired T cell function was mediated by factor(s) released by live TDCs after direct interaction with lymphocytes. Also, the TDC-induced effect on T cells was markedly reduced by blocking of NADPH oxidase but not by inhibition of arginase, inducible NO synthase (iNOS), IDO, or IFN-gamma. Moreover, we found that hyaluronan fragments constituted a common factor produced by a variety of human tumor cell lines to induce formation of TDCs. These observations indicate that tumor microenvironments, including hyaluronan fragments derived from cancer cells, educate DCs to adopt a semimature phenotype, which in turn...Continue Reading

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Citations

Nov 11, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Dong-Ming KuangLimin Zheng
Mar 5, 2014·Proceedings of the National Academy of Sciences of the United States of America·Wen-Chao WuLimin Zheng
Sep 23, 2014·The Journal of Clinical Investigation·Dong-Ming KuangLimin Zheng
Aug 23, 2020·International Journal of Molecular Sciences·Jinfen WeiHongli Du
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Jun 29, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Dong-Ming KuangLimin Zheng
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Aug 4, 2015·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Rui-Xian LiuDong-Ming Kuang
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Sep 18, 2020·Cellular and Molecular Life Sciences : CMLS·Yuan WeiDong-Ming Kuang

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