Blocking immunosuppressive neutral granulocytes can inhibit brain metastasis!

brain metastasis, which occurs in many cancers, is an ominous discovery that is still difficult to treat. Treating these metastasis tumors is challenging, and their micro-environments have not been well studied as peripheral cancers.The role of immune cells in brain metastasis is unclear, as the brain has traditionally been considered to have "immune privileges". Recently, researchers from the MD Anderson Cancer Center at the University of Texas, the UTHealth Biomedical Research Institute at the MD Anderson Cancer Center, and the Molecular Medicine Center at China Medical University in Taiwan, led by Professor Dihua Yu, discovered an oscic genetic modification protein called ZESTE congener 2 (EZH2) that is over-expressed in brain metastases, stimulating signaling paths to recruit immunosuppressive neutral granulocytes into tumors. The findings, published recently in Science Translational Medicine, are entitled "Blocking immunosuppressive neutrophils deters pY696-EZH2-drive brain metastases".For the study, researchers found that a group of immunosuppressive neutral granulocytes were recruited into the brain to allow brain metastasis to develop. In brain metastasis cells, EZH2 is highly expressed by nuclearly located Src tyrosine kinase and phosphates at tyrosine-696 (pY696) -EZH2 bits.The researchers found that phosphatization of EZH2 at Y696 site changed its binding preference from histoprotein H3 to RNA polymerase II, transforming the function of EZH2 from methyl transferase to a transcription factor that increases c-JUN expression. c-Jun can increase carcinogenic inflammatory cytokines, including granulocyte colony stimulation factors (G-CSF), which recruit Amg1-plus and PD-L1-Immune-inhibited neastatic granulocytes into the brain to facilitate metastasis.The researchers found in several mouse models that G-CSF blocking antibodies or immuno-checkpoint blocking therapy combined with Src inhibitors to inhibit brain metastasis. These results show that pY696-EZH2 can promote immunosuppressive brain immersion of neutral granulocytes as an irrelevant transcription factor of methyl transferase, and can be used as a clinical target for the treatment of brain metastasis. (Bio Valley Bioon .com)