Blocking immunosuppressive neutrophils deters pY696-EZH2–driven brain metastases
Lin Zhang, Jun Yao, Yongkun Wei, Zhifen Zhou, Ping Li, Jingkun Qu, Akosua Badu-Nkansah, Xiangliang Yuan, Yu-Wen Huang, Kazutaka Fukumura, Xizeng Mao, Wei-Chao Chang, Jodi M. Saunus, Sunil R. Lakhani, Jason T. Huse, Mien‐Chie Hung, Dihua Yu
Abstract
immunosuppressive neutrophils into the brain to drive metastasis outgrowth. G-CSF-blocking antibodies or immune checkpoint blockade therapies combined with Src inhibitors impeded brain metastasis in multiple mouse models. These findings indicate that pY696-EZH2 can function as a methyltransferase-independent transcription factor to facilitate the brain infiltration of immunosuppressive neutrophils, which could be clinically targeted for brain metastasis treatment.
Topics & Concepts
BlockadeInfiltration (HVAC)Blocking (statistics)Immune checkpointAntibodyImmune systemBrain metastasisBlock (permutation group theory)Blocking antibodyImmunologyCancer researchMedicineReceptorMetastasisCancerInternal medicinePhysicsMathematicsThermodynamicsStatisticsGeometryEpigenetics and DNA MethylationImmune cells in cancerFerroptosis and cancer prognosis