Unsynchronized butyrophilin molecules dictate cancer cell evasion of Vγ9Vδ2 T-cell killing.

Autor: Wu Z; Biomedical Pioneering Innovation Center, Peking-Tsinghua Center for Life Sciences, Peking University Genome Editing Research Center, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, 100871, Beijing, China., Lamao Q; Biomedical Pioneering Innovation Center, Peking-Tsinghua Center for Life Sciences, Peking University Genome Editing Research Center, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, 100871, Beijing, China., Gu M; Biomedical Pioneering Innovation Center, Peking-Tsinghua Center for Life Sciences, Peking University Genome Editing Research Center, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, 100871, Beijing, China., Jin X; Biomedical Pioneering Innovation Center, Peking-Tsinghua Center for Life Sciences, Peking University Genome Editing Research Center, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, 100871, Beijing, China., Liu Y; Biomedical Pioneering Innovation Center, Peking-Tsinghua Center for Life Sciences, Peking University Genome Editing Research Center, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, 100871, Beijing, China., Tian F; Biomedical Pioneering Innovation Center, Peking-Tsinghua Center for Life Sciences, Peking University Genome Editing Research Center, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, 100871, Beijing, China., Yu Y; Biomedical Pioneering Innovation Center, Peking-Tsinghua Center for Life Sciences, Peking University Genome Editing Research Center, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, 100871, Beijing, China., Yuan P; EdiGene Inc., Life Science Park, Changping District, 102206, Beijing, China., Gao S; Center for Precision Medicine Multi-Omics Research, Peking University Health Science Center, Peking University, 100191, Beijing, China., Fulford TS; Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, VIC, 3010, Australia., Uldrich AP; Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, VIC, 3010, Australia.; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia., Wong CC; State Key Laboratory for Complex, Severe and Rare Diseases, Clinical Research Institute, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Peking-Tsinghua Center for Life Sciences, 100871, Beijing, China. catclw321@126.com., Wei W; Biomedical Pioneering Innovation Center, Peking-Tsinghua Center for Life Sciences, Peking University Genome Editing Research Center, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, 100871, Beijing, China. wswei@pku.edu.cn.
Jazyk: angličtina
Zdroj: Cellular & molecular immunology [Cell Mol Immunol] 2024 Apr; Vol. 21 (4), pp. 362-373. Date of Electronic Publication: 2024 Feb 20.
DOI: 10.1038/s41423-024-01135-z
Abstrakt: 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-γ signaling 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.
(© 2024. The Author(s), under exclusive licence to CSI and USTC.)
Databáze: MEDLINE
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