Granzyme B degradation by autophagy decreases tumor cell susceptibility to natural killer-mediated lysis under hypoxia

Baginska J.; Viry E.; Berchem G.Poli A.Noman M.Z.Van Moer K.Medves S.Zimmer J.Oudin A.Niclou S.P.Bleackley R.C.Goping I.S.Chouaib S.Janji B.

首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Granzyme B degradation by autophagy decreases tumor cell susceptibility to natural killer-mediated lysis under hypoxia

【24h】

Granzyme B degradation by autophagy decreases tumor cell susceptibility to natural killer-mediated lysis under hypoxia

机译：Granzyme B degradation by autophagy decreases tumor cell susceptibility to natural killer-mediated lysis under hypoxia

获取原文

获取原文并翻译 | 示例

掌桥外文数据库（机构版） >>

开具论文收录证明 >>

文献代查 >>

页面导航

摘要
著录项
相关主题

摘要

Recent studies demonstrated that autophagy is an important regulator of innate immune response. However, the mechanism by which autophagy regulates natural killer (NK) cell-mediated antitumor immune responses remains elusive. Here,we demonstrate that hypoxia impairs breast cancer cell susceptibility to NK-mediated lysis in vitro via the activation of autophagy. This impairment was not related to a defect in target cell recognition by NK cells but to the degradation of NK-derived granzyme B in autophagosomes of hypoxic cells. Inhibition of autophagy by targeting beclin1 (BECN1) restored granzyme B levels in hypoxic cells in vitro and induced tumor regression in vivo by facilitating NK-mediated tumor cell killing. Together, our data highlight autophagy as a mechanism underlying the resistance of hypoxic tumor cells to NK-mediated lysis. The work presented here provides a cutting-edge advance in our understanding of the mechanism by which hypoxia-induced autophagy impairs NK-mediated lysis in vitro and paves the way for the formulation of more effective NK cell-based antitumor therapies.

著录项

来源
《Proceedings of the National Academy of Sciences of the United States of America》 |2013年第43期|17450-17455|共6页
作者
Baginska J.; Viry E.; Berchem G.Poli A.Noman M.Z.Van Moer K.Medves S.Zimmer J.Oudin A.Niclou S.P.Bleackley R.C.Goping I.S.Chouaib S.Janji B.;
展开▼
作者单位

Laboratory of Experimental Hemato-Oncology, Department of Oncology, Public Research Center for Health, L-1526 Luxembourg City, Luxembourg;

Laboratory of Immunogenetics and Allergology, Public Research Center for Health, L-1526 Luxembourg City, Luxembourg;

Institut National de la Santé et de la Recherche Médicale, Institut de Cancérologie Gustave Roussy, F-94805 Villejuif Cedex, FranceDepartment of Oncology, Neuro-Oncology Laboratory, Public Research Center for Health, L-1526 Luxembourg City, LuxembourgDepartment of Biochemistry, University of Alberta, Edmonton, AB T6G 2H7, Canada;

展开▼
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
正文语种英语
中图分类自然科学总论;
关键词
Breast adenocarcinoma; Hypoxic tumor microenvironment; Immunotherapy; Innate immunity;

Granzyme B degradation by autophagy decreases tumor cell susceptibility to natural killer-mediated lysis under hypoxia

摘要

著录项

相关主题

期刊订阅