Science sub-published a new breakthrough! Blocking immunosuppressed neutrophils can inhibit brain metastasis!

, June 16, 2020 /PRNewswire/ --BiovalleyBIOON/-- Brain metastasis, which occurs in many cancers, is an ominous discovery that is still difficult to treatThe treatment of these metastatictumoris challenging, and their microenvironments have not been studied as well as peripheral cancersthe role ofimmune cells in brain metastasis is unclear, as the brain is traditionally considered to have "immune privileges"Recently, researchers from the University of Texas MD Anderson Cancer Center, MD Anderson Cancer Center UTHealth Biomedical Research Institute, Taiwan China Medical University Molecular Medicine Center and other units, led by Professor Dihua Yu, found a epigeneticgeneticmodified protein called ZESTE homologous enhancer 2 (
EZH2) in the brain metastatic tumor, which stimulates the signaling pathway to recruit immunoneutral cells intotumorsThe results of the study, published recently in Science Translational Medicine, are entitled "Blocking Immunosuppressive neutrophils deters pY696-
EZH2-driven brain metastases" Picture Source: In the study, Science Translational Medicine researchers found that a group of immunosuppressive neutrophils were recruited into the brain to allow brain metastasis to develop In brain metastasis cells, EZH2 is highly expressed by approved src tyrosine kinase and phosphorylation occurs at the site of tyrosine-696 (pY696) - EZH2 researchers found that phosphorylation of EZH2 at Y696 site changed its binding preference, moving from histone H3 to RNA polymerase II, thus The function of EZH2 changes from methyl transferase to transcription factor that increases c-JUN expression c-Jun raises the carcinogenic inflammatory cytokine, including granulocyte syinvasive stimulator (G-CSF), which recruits Arg1 plus- and PD-L1-plus immunosuppressive neutrophils into the brain to facilitate metastasis researchers found in several mouse models that G-CSF blocking antibodies or immunocheckpoint blocking therapy in combination with Src inhibitors can inhibit brain metastasis These results show that pY696-
EZH2 can be used as an irrepresso-related transcription factor of methyl metase to promote brain immersion of immunosuppressed neutrophils and can be used as a clinical target for the treatment of brain metastasis (BioValleyBioon.com) References: Dihua Yu et al.
Blocking immunosuppressive neutrophils deters pY696-EZH2-driven brain metastases Science Translational Medicine 27 May 2020: Vol 12, Issue 545, eaaz5387 DOI: 10.1126/scitranslmed.aaz5387