NKG2D公司
免疫监视
表皮生长因子受体
细胞溶解
细胞生物学
生物
癌症研究
免疫疗法
受体
表皮生长因子
免疫学
免疫系统
细胞毒性T细胞
体外
生物化学
作者
Pierre Vantourout,Carrie R. Willcox,Andrea Turner,Chad M. Swanson,Yasmin Haque,Olga Sobolev,Anita Grigoriadis,Andrew Tutt,Adrian Hayday
出处
期刊:Science Translational Medicine
[American Association for the Advancement of Science (AAAS)]
日期:2014-04-09
卷期号:6 (231)
被引量:49
标识
DOI:10.1126/scitranslmed.3007579
摘要
Human cytolytic T lymphocytes and natural killer cells can limit tumor growth and are being increasingly harnessed for tumor immunotherapy. One way cytolytic lymphocytes recognize tumor cells is by engagement of their activating receptor, NKG2D, by stress antigens of the MICA/B and ULBP families. This study shows that surface up-regulation of NKG2D ligands by human epithelial cells in response to ultraviolet irradiation, osmotic shock, oxidative stress, and growth factor provision is attributable to activation of the epidermal growth factor receptor (EGFR). EGFR activation causes intracellular relocalization of AUF1 proteins that ordinarily destabilize NKG2D ligand mRNAs by targeting an AU-rich element conserved within the 3' ends of most human, but not murine, NKG2D ligand genes. Consistent with these findings, NKG2D ligand expression by primary human carcinomas positively correlated with EGFR expression, which is commonly hyperactivated in such tumors, and was reduced by clinical EGFR inhibitors. Therefore, stress-induced activation of EGFR not only regulates cell growth but also concomitantly regulates the cells' immunological visibility. Thus, therapeutics designed to limit cancer cell growth should also be considered in terms of their impact on immunosurveillance.
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