Radiotherapy orchestrates natural killer cell dependent antitumor immune responses through CXCL8.


Thomas Walle, Joscha A Kraske, Boyu Liao, Bénédicte Lenoir, Carmen Timke, Emilia von Bohlen Und Halbach, Florian Tran, Paul Griebel, Dorothee Albrecht, Azaz Ahmed, Meggy Suarez-Carmona, Alejandro Jiménez-Sánchez, Tizian Beikert, Alexandra Tietz-Dahlfuß, Ayse Nur Menevse, Gabriele Schmidt, Manuela Brom, Jens H W Pahl, Wiebke Antonopoulos, Matthias Miller, Ramon Lopez Perez, Felix Bestvater, Nathalia A Giese, Philipp Beckhove, Philip Rosenstiel, Dirk Jäger, Oliver Strobel, Dana Pe’er, Niels Halama, Jürgen Debus, Adelheid Cerwenka, Peter E Huber

Year of publication



Sci Adv







Impact factor



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.