Journal Article

DKFZ-2022-00529

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Radiotherapy orchestrates natural killer cell dependent antitumor immune responses through CXCL8.

Walle, T. (First author)DKFZ* ; Kraske, J.DKFZ* ; Liao, B.DKFZ* ; Lenoir, B.DKFZ* ; Timke, C. ; von Bohlen Und Halbach, E.DKFZ* ; Tran, F. ; Griebel, P. ; Albrecht, D.DKFZ* ; Ahmed, A.DKFZ* ; Suarez-Carmona, M.DKFZ* ; Jiménez-Sánchez, A. ; Beikert, T.DKFZ* ; Tietz-Dahlfuß, A.DKFZ* ; Menevse, A. N. ; Schmidt, G.DKFZ* ; Brom, M.DKFZ* ; Pahl, J. H. W. ; Antonopoulos, W. ; Miller, M. ; Perez, R. L.DKFZ* ; Bestvater, F.DKFZ* ; Giese, N. A. ; Beckhove, P. ; Rosenstiel, P. ; Jäger, D.DKFZ* ; Strobel, O. ; Pe'er, D. ; Halama, N.DKFZ* ; Debus, J. ; Cerwenka, A. ; Huber, P. (Last author)DKFZ*

2022
Assoc. Washington, DC [u.a.]

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Please use a persistent id in citations: doi:10.1126/sciadv.abh4050

Abstract: 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.

Note: #EA:E055#LA:E055#

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Contributing Institute(s):

1. E055 KKE Translationale Radioonkologie (E055)
2. DKTK HD zentral (HD01)
3. D120 Angewandte Tumor-Immunität (D120)
4. Translationale Immuntherapie (D240)
5. Lichtmikroskopie (W210)

Research Program(s):

1. 315 - Bildgebung und Radioonkologie (POF4-315) (POF4-315)

Appears in the scientific report 2022

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Database coverage:
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