Radiotherapy orchestrates natural killer cell dependent antitumor immune responses through CXCL8 Journal Article
| Authors: | Walle, T.; Kraske, J. A.; Liao, B.; Lenoir, B.; Timke, C.; Von Bohlen und Halbach, E.; Tran, F.; Griebel, P.; Albrecht, D.; Ahmed, A.; Suarez-Carmona, M.; Jiménez-Sánchez, A.; Beikert, T.; Tietz-Dahlfuß, A.; Menevse, A. N.; Schmidt, G.; Brom, M.; Pahl, J. H. W.; Antonopoulos, W.; Miller, M.; Perez, R. L.; Bestvater, F.; Giese, N. A.; Beckhove, P.; Rosenstiel, P.; Jäger, D.; Strobel, O.; Pe'er, D.; Halama, N.; Debus, J.; Cerwenka, A.; Huber, P. E. |
| Article Title: | Radiotherapy orchestrates natural killer cell dependent antitumor immune responses through CXCL8 |
| Abstract: | 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. © 2022 American Association for the Advancement of Science. All rights reserved. |
| Keywords: | controlled study; overall survival; mouse; animal; cytology; animals; mice; immune system; randomized controlled trial; radiotherapy; interleukin 8; cancer therapy; immune response; interleukin-8; tumors; natural killer cell; adoptive transfer; killer cells, natural; immunity; mammals; diseases; t-cells; t-cell response; radiation-induced; pancreatic cancers; natural killer cells; pancreatic tumors; anti-tumor immune; antitumor effect |
| Journal Title: | Science Advances |
| Volume: | 8 |
| Issue: | 12 |
| ISSN: | 2375-2548 |
| Publisher: | Amer Assoc Advancement Science |
| Date Published: | 2022-03-25 |
| Start Page: | eabh4050 |
| Language: | English |
| DOI: | 10.1126/sciadv.abh4050 |
| PUBMED: | 35319989 |
| PROVIDER: | scopus |
| PMCID: | PMC8942354 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 May 2022 -- Source: Scopus |
