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. Accordingly, NK cells preferentially infiltrated irradiated pancreatic tumors and exhibited CD56 dim-like cytotoxic transcriptomic states. In a randomized controlled pancreatic cancer trial, CXCL8 increased under radiotherapy, and NK cell positively correlated with prolonged overall survival. 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. However, the role of Natural Killer (NK) cells in radiotherapy remains unclear. Radiotherapy is a mainstay cancer therapy whose antitumor effects partially depend on T cell responses. Giese, Philipp Beckhove, Philip Rosenstiel, Dirk Jäger, Oliver Strobel, Dana Pe’er, Niels Halama, Jürgen Debus, Adelheid Cerwenka, and Peter E. Pahl, Wiebke Antonopoulos, Matthias Miller, Ramon Lopez Perez, Felix Bestvater, Nathalia A. Kraske, Boyu Liao, Bénédicte Lenoir, Carmen Timke, Emilia von Bohlen und Halbach, Florian Tran, … Show All …, 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.
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