Radiotherapy orchestrates natural killer cell dependent antitumor immune responses through CXCL8

Walle T, Kraske JA, Liao B, Lenoir B, Timke C, Halbach EVBU, Tran F, Griebel P, Albrecht D, Ahmed A, Suarez-Carmona M, Jimenez-Sanchez A, Beikert T, Tietz-Dahlfuss A, Menevse AN, Schmidt G, Brom M, Pahl JHW, Antonopoulos W, Miller M, Perez RL, Bestvater F, Giese NA, Beckhove P, Rosenstiel P, Jaeger D, Strobel O, Pe'Er D, Halama N, Debus J, Cerwenka A, Huber PE (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Science Advances American Association for the Advancement of Science

Book Volume: 8

Article Number: eabh4050

Journal Issue: 12

DOI: 10.1126/sciadv.abh4050

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.

Involved external institutions

Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) Christian-Albrechts-Universität zu Kiel DE Germany (DE) Memorial Sloan Kettering Cancer Center US United States (USA) (US) Leibniz-Institut für Immuntherapie (LIT) / Leibniz Institute for Immunotherapy DE Germany (DE) Ruprecht-Karls-Universität Heidelberg DE Germany (DE) Universitätsklinikum Heidelberg DE Germany (DE)

How to cite

APA:

Walle, T., Kraske, J.A., Liao, B., Lenoir, B., Timke, C., Halbach, E.V.B.U.,... Huber, P.E. (2022). Radiotherapy orchestrates natural killer cell dependent antitumor immune responses through CXCL8. Science Advances, 8(12). https://doi.org/10.1126/sciadv.abh4050

MLA:

Walle, Thomas, et al. "Radiotherapy orchestrates natural killer cell dependent antitumor immune responses through CXCL8." Science Advances 8.12 (2022).

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