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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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  • Media type: E-Article
  • Title: Radiotherapy orchestrates natural killer cell dependent antitumor immune responses through CXCL8
  • Contributor: 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; [...]
  • Published: American Association for the Advancement of Science (AAAS), 2022
  • Published in: Science Advances, 8 (2022) 12
  • Language: English
  • DOI: 10.1126/sciadv.abh4050
  • ISSN: 2375-2548
  • Origination:
  • Footnote:
  • Description: 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 dim -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 dim 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.
  • Access State: Open Access