期刊
SCIENCE ADVANCES
卷 8, 期 12, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abh4050
关键词
-
资金
- Deutsche Krebshilfe e.V. (German Cancer Aid) [111582, 111455, GRK2099]
- DKFZ Clinician Scientist Program
- Dieter Morszeck Foundation
- Merck KGaA, Darmstadt, Germany
- Kompetenzverbund Strahlenforschung (KVSF) of the German Ministries for Education, Research and Environment, Bundesministerien fur Bildung, Forschung und Umwelt (BMBF/BMU) [03NUK004A]
- German Research Foundation [SFB1366, 394046768-SFB 1366, SPP 1937 (CE 140/2-2), TRR179 (TP07), SFB-TRR156 (B10N), RTG 2099, 259332240-RTG2099]
- European Commission [H2020-MSCA-MC-ITN-765104MATURE-NK]
NK cells play a central role in the radiation-induced immune response, enhancing tumor control through the secretion of CXCL8/IL-8 and recruiting immune cells. This discovery suggests a rational cancer treatment strategy combining NK cells with radiotherapy.
Radiotherapy is a mainstay cancer therapy whose antitumor effects partially depend on T cell responses. However, the role of Natural Killer (NK) cells in radiotherapy remains unclear. Here, using a reverse translational approach, we show a central role of NK cells in the radiation-induced immune response involving a CXCL8/IL-8-dependent mechanism. In a randomized controlled pancreatic cancer trial, CXCL8 increased under radiotherapy, and NK cell positively correlated with prolonged overall survival. Accordingly, NK cells preferentially infiltrated irradiated pancreatic tumors and exhibited CD56(dim)-like cytotoxic transcriptomic states. In experimental models, NF-kappa B and mTOR orchestrated radiation-induced CXCL8 secretion from tumor cells with senescence features causing directional migration of CD56(dim) NK cells, thus linking senescence-associated CXCL8 release to innate immune surveillance of human tumors. Moreover, combined high-dose radiotherapy and adoptive NK cell transfer improved tumor control over monotherapies in xenografted mice, suggesting NK cells combined with radiotherapy as a rational cancer treatment strategy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据