TY  - JOUR
AU  - Walle, Thomas
AU  - Kraske, Joscha
AU  - Liao, Boyu
AU  - Lenoir, Bénédicte
AU  - Timke, Carmen
AU  - von Bohlen Und Halbach, Emilia
AU  - Tran, Florian
AU  - Griebel, Paul
AU  - Albrecht, Dorothee
AU  - Ahmed, Azaz
AU  - Suarez-Carmona, Meggy
AU  - Jiménez-Sánchez, Alejandro
AU  - Beikert, Tizian
AU  - Tietz-Dahlfuß, Alexandra
AU  - Menevse, Ayse Nur
AU  - Schmidt, Gabriele
AU  - Brom, Manuela
AU  - Pahl, Jens H W
AU  - Antonopoulos, Wiebke
AU  - Miller, Matthias
AU  - Perez, Ramon Lopez
AU  - Bestvater, Felix
AU  - Giese, Nathalia A
AU  - Beckhove, Philipp
AU  - Rosenstiel, Philip
AU  - Jäger, Dirk
AU  - Strobel, Oliver
AU  - Pe'er, Dana
AU  - Halama, Niels
AU  - Debus, Jürgen
AU  - Cerwenka, Adelheid
AU  - Huber, Peter
TI  - Radiotherapy orchestrates natural killer cell dependent antitumor immune responses through CXCL8.
JO  - Science advances
VL  - 8
IS  - 12
SN  - 2375-2548
CY  - Washington, DC [u.a.]
PB  - Assoc.
M1  - DKFZ-2022-00529
SP  - eabh4050
PY  - 2022
N1  - #EA:E055#LA:E055#
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:35319989
DO  - DOI:10.1126/sciadv.abh4050
UR  - https://inrepo02.dkfz.de/record/179247
ER  -