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Walle, Thomas; Kraske, Joscha A.; Liao, Boyu; Lenoir, Bénédicte; Timke, Carmen; von Bohlen und Halbach, Emilia; Tran, Florian; Griebel, Paul; Albrecht, Dorothee; Ahmed, Azaz; Suarez-Carmona, Meggy; Jiménez-Sánchez, Alejandro; Beikert, Tizian; Tietz-Dahlfuß, Alexandra; Menevse, Ayse Nur; Schmidt, Gabriele; Brom, Manuela; Pahl, Jens H. W.; Antonopoulos, Wiebke; Miller, Matthias; Perez, Ramon Lopez; Bestvater, Felix; Giese, Nathalia A.; Beckhove, Philipp; [...]

Radiotherapy orchestrates natural killer cell dependent antitumor immune responses through CXCL8

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  • Medientyp: E-Artikel
  • Titel: Radiotherapy orchestrates natural killer cell dependent antitumor immune responses through CXCL8
  • Beteiligte: Walle, Thomas; Kraske, Joscha A.; Liao, Boyu; Lenoir, Bénédicte; Timke, Carmen; von Bohlen und Halbach, Emilia; Tran, Florian; Griebel, Paul; Albrecht, Dorothee; Ahmed, Azaz; Suarez-Carmona, Meggy; Jiménez-Sánchez, Alejandro; Beikert, Tizian; Tietz-Dahlfuß, Alexandra; Menevse, Ayse Nur; Schmidt, Gabriele; Brom, Manuela; Pahl, Jens H. W.; Antonopoulos, Wiebke; Miller, Matthias; Perez, Ramon Lopez; Bestvater, Felix; Giese, Nathalia A.; Beckhove, Philipp; [...]
  • Erschienen: American Association for the Advancement of Science (AAAS), 2022
  • Erschienen in: Science Advances
  • Sprache: Englisch
  • DOI: 10.1126/sciadv.abh4050
  • ISSN: 2375-2548
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:p> 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 CD56 <jats:sup>dim</jats:sup> -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 CD56 <jats:sup>dim</jats:sup> 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. </jats:p>
  • Zugangsstatus: Freier Zugang