D-mannose facilitates immunotherapy and radiotherapy of triple-negative breast cancer via degradation of PD-L1

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  • Ruonan Zhang
    Ministry of Education Key Laboratory of Metabolism and Molecular Medicine, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
  • Yajing Yang
    Ministry of Education Key Laboratory of Metabolism and Molecular Medicine, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
  • Wenjing Dong
    Ministry of Education Key Laboratory of Metabolism and Molecular Medicine, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
  • Mingen Lin
    Ministry of Education Key Laboratory of Metabolism and Molecular Medicine, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
  • Jing He
    Ministry of Education Key Laboratory of Metabolism and Molecular Medicine, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
  • Xinchao Zhang
    Ministry of Education Key Laboratory of Metabolism and Molecular Medicine, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
  • Tongguan Tian
    Tongji Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai 200120, China
  • Yunlong Yang
    Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
  • Kun Chen
    Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Translational Medical Center for Stem Cell Therapy, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200120, China
  • Qun-Ying Lei
    Fudan University Shanghai Cancer Center and Cancer Metabolism Laboratory, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China
  • Song Zhang
    Institute for Immunology and College of Life Sciences, Nankai University, Tianjin 300071, China
  • Yanping Xu
    Tongji Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai 200120, China
  • Lei Lv
    Ministry of Education Key Laboratory of Metabolism and Molecular Medicine, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China

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<jats:title>Significance</jats:title> <jats:p>PD-L1 is well known as an immune checkpoint molecule, which suppresses immune surveillance through binding to its receptor PD-1. Intracellular PD-L1 can also protect messenger RNAs of several DNA damage repair–related genes from degradation and enhance tumor resistance to DNA-damaging therapy. Triple-negative breast cancer (TNBC) has the worst prognosis and highest risk of distant relapse in breast cancer and shows resistance to immunotherapy and radiotherapy. In this study, we found that D-mannose can promote the degradation of PD-L1 and significantly enhance immunotherapy and radiotherapy of TNBC. Since TNBC treatment is still a clinical challenge, our findings provide strategies to enhance the therapeutic efficacy of TNBC and may have clinical application.</jats:p>

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