Vγ9Vδ2 T cells are specialized effector cells that have gained prominence as immunotherapy agents due to their ability to target and kill cells with altered pyrophosphate metabolites.In our effort to understand how ...Vγ9Vδ2 T cells are specialized effector cells that have gained prominence as immunotherapy agents due to their ability to target and kill cells with altered pyrophosphate metabolites.In our effort to understand how cancer cells evade the cell-killing activity of Vγ9Vδ2 T cells,we performed a comprehensive genome-scale CRISPR screening of cancer cells.We found that four molecules belonging to the butyrophilin(BTN)family,specifically BTN2A1,BTN3A1,BTN3A2,and BTN3A3,are critically important and play unique,nonoverlapping roles in facilitating the destruction of cancer cells by primary Vγ9Vδ2 T cells.The coordinated function of these BTN molecules was driven by synchronized gene expression,which was regulated by IFN-γsignaling and the RFX complex.Additionally,an enzyme called QPCTL was shown to play a key role in modifying the N-terminal glutamine of these BTN proteins and was found to be a crucial factor in Vγ9Vδ2 T cell killing of cancer cells.Through our research,we offer a detailed overview of the functional genomic mechanisms that underlie how cancer cells escape Vγ9Vδ2 T cells.Moreover,our findings shed light on the importance of the harmonized expression and function of gene family members in modulating T-cell activity.展开更多
Dear Editor,X-linked sideroblastic anemia(XLSA),which is the most common genetic form of congenital sideroblastic anemia,is typically characterized by reduced heme synthesis and the presence of bone marrow(BM)ring sid...Dear Editor,X-linked sideroblastic anemia(XLSA),which is the most common genetic form of congenital sideroblastic anemia,is typically characterized by reduced heme synthesis and the presence of bone marrow(BM)ring sideroblasts containing pathologic iron deposits in the mitochondria.展开更多
基金funding from the National Science Foundation of China(31930016)the Peking-Tsinghua Center for Life Sciences+4 种基金ZW received funding from the State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases(2024KF00001)the National Science Foundation of China(82350119)CCW received funding from the Talent Introduction Funds from the Chinese Academy of Medical Science(2022-RC310-10)the National Science Foundation of China(32150005)the Research Funds from Health@InnoHK Program,launched by the Innovation Technology Commission of the Hong Kong Special Administrative Region.
文摘Vγ9Vδ2 T cells are specialized effector cells that have gained prominence as immunotherapy agents due to their ability to target and kill cells with altered pyrophosphate metabolites.In our effort to understand how cancer cells evade the cell-killing activity of Vγ9Vδ2 T cells,we performed a comprehensive genome-scale CRISPR screening of cancer cells.We found that four molecules belonging to the butyrophilin(BTN)family,specifically BTN2A1,BTN3A1,BTN3A2,and BTN3A3,are critically important and play unique,nonoverlapping roles in facilitating the destruction of cancer cells by primary Vγ9Vδ2 T cells.The coordinated function of these BTN molecules was driven by synchronized gene expression,which was regulated by IFN-γsignaling and the RFX complex.Additionally,an enzyme called QPCTL was shown to play a key role in modifying the N-terminal glutamine of these BTN proteins and was found to be a crucial factor in Vγ9Vδ2 T cell killing of cancer cells.Through our research,we offer a detailed overview of the functional genomic mechanisms that underlie how cancer cells escape Vγ9Vδ2 T cells.Moreover,our findings shed light on the importance of the harmonized expression and function of gene family members in modulating T-cell activity.
基金This work was supported by grants from the Ministry of Science and Technology of China(2019YFA0110803)the CAMS Innovation Fund for Medical Sciences(2016-I2M-1-002 and 2019-12M-1-006)the National Nature Science Foundation of China(81890992,81670112 and 81770175,82070201).
文摘Dear Editor,X-linked sideroblastic anemia(XLSA),which is the most common genetic form of congenital sideroblastic anemia,is typically characterized by reduced heme synthesis and the presence of bone marrow(BM)ring sideroblasts containing pathologic iron deposits in the mitochondria.