%0 Journal Article
%A Walle, Thomas
%A Kraske, Joscha
%A Liao, Boyu
%A Lenoir, Bénédicte
%A Timke, Carmen
%A von Bohlen Und Halbach, Emilia
%A Tran, Florian
%A Griebel, Paul
%A Albrecht, Dorothee
%A Ahmed, Azaz
%A Suarez-Carmona, Meggy
%A Jiménez-Sánchez, Alejandro
%A Beikert, Tizian
%A Tietz-Dahlfuß, Alexandra
%A Menevse, Ayse Nur
%A Schmidt, Gabriele
%A Brom, Manuela
%A Pahl, Jens H W
%A Antonopoulos, Wiebke
%A Miller, Matthias
%A Perez, Ramon Lopez
%A Bestvater, Felix
%A Giese, Nathalia A
%A Beckhove, Philipp
%A Rosenstiel, Philip
%A Jäger, Dirk
%A Strobel, Oliver
%A Pe'er, Dana
%A Halama, Niels
%A Debus, Jürgen
%A Cerwenka, Adelheid
%A Huber, Peter
%T Radiotherapy orchestrates natural killer cell dependent antitumor immune responses through CXCL8.
%J Science advances
%V 8
%N 12
%@ 2375-2548
%C Washington, DC [u.a.]
%I Assoc.
%M DKFZ-2022-00529
%P eabh4050
%D 2022
%Z #EA:E055#LA:E055#
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:35319989
%R 10.1126/sciadv.abh4050
%U https://inrepo02.dkfz.de/record/179247