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| 001 | 179247 | ||
| 005 | 20240229145537.0 | ||
| 024 | 7 | _ | |a 10.1126/sciadv.abh4050 |2 doi |
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| 100 | 1 | _ | |a Walle, Thomas |0 P:(DE-He78)51635089578f68fc9efdb61e6a760b64 |b 0 |e First author |u dkfz |
| 245 | _ | _ | |a Radiotherapy orchestrates natural killer cell dependent antitumor immune responses through CXCL8. |
| 260 | _ | _ | |a Washington, DC [u.a.] |c 2022 |b Assoc. |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 520 | _ | _ | |a 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 CD56dim-like cytotoxic transcriptomic states. In experimental models, NF-κB and mTOR orchestrated radiation-induced CXCL8 secretion from tumor cells with senescence features causing directional migration of CD56dim 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. |
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| 700 | 1 | _ | |a Timke, Carmen |0 0000-0003-0256-6625 |b 4 |
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| 700 | 1 | _ | |a Griebel, Paul |0 0000-0001-5671-8183 |b 7 |
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| 700 | 1 | _ | |a Antonopoulos, Wiebke |b 18 |
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| 700 | 1 | _ | |a Perez, Ramon Lopez |0 0000-0002-6876-2074 |b 20 |
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| 700 | 1 | _ | |a Beckhove, Philipp |b 23 |
| 700 | 1 | _ | |a Rosenstiel, Philip |0 0000-0002-9692-8828 |b 24 |
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| 700 | 1 | _ | |a Strobel, Oliver |b 26 |
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| 700 | 1 | _ | |a Huber, Peter |0 P:(DE-He78)3291aaac20f3d603d96744c1f0890028 |b 31 |e Last author |u dkfz |
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