放疗通过 CXCL8 调控 NK 细胞依赖性抗肿瘤免疫应答

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- B 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.