Radiotherapy orchestrates natural killer cell dependent antitumor immune responses through CXCL8
Menée à l'aide de xénogreffes sur des modèles murins et d'échantillons sanguins prélevés sur des patients atteints d'un cancer du pancréas ou sur des donneurs sains, cette étude met en évidence un mécanisme par lequel les rayonnements ionisants, en induisant la sécrétion de l'interleukine CXCL8 et le recrutement intratumoral de certaines cellules NK, favorisent la réponse immunitaire antitumorale
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.
Science Advances 2022