DNA damage induced by CDK4 and CDK6 blockade triggers anti-tumor immune responses through cGAS-STING pathway

• DOI: 10.1038/s42003-023-05412-x
• Publication Date: 2023-10-13T18:02:13Z
• Authors: Huimin Fan; Wancheng Liu; Yanqiong Zeng; Ying Zhou; Meiling Gao; Liping Yang; Hao Liu; Yueyue Shi; Lili Li; Jiayuan Ma; Jiayin Ruan; Ruyun Cao; Xiaoxia Jin; Jian Chen; Genhong Cheng; Heng Yang
• Keywords: Cyclin-dependent kinase 6; Sting

CDK4/6 are important regulators of cell cycle and their inhibitors have been approved as anti-cancer drugs. Here, we report a STING-dependent anti-tumor immune mechanism responsible for tumor suppression by blockade. Clinical datasets show that in human tissues, CDK4 CDK6 over-expressed expressions negatively correlated with patients' overall survival T infiltration. Deletion Cdk4 or Cdk6 cells significantly reduce growth. Mechanistically, find deficiency contributes to an increased level endogenous DNA damage, which triggers the cGAS-STING signaling pathway activate type I interferon response. Knockout Sting is sufficient reverse partially effect respectively. Therefore, our findings suggest may enhance immunity through