Browsing by Author "Wang, Xiyu"

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    Metabolic interventions: A new insight into the cancer immunotherapy
    (Elsevier, 2021) Yu, Tao; Dong, Tianhan; Eyvani, Haniyeh; Fang, Yuanzhang; Wang, Xiyu; Zhang, Xinna; Lu, Xiongbin; Medical and Molecular Genetics, School of Medicine
    Metabolic reprogramming confers cancer cells plasticity and viability under harsh conditions. Such active alterations lead to cell metabolic dependency, which can be exploited as an attractive target in development of effective antitumor therapies. Similar to cancer cells, activated T cells also execute global metabolic reprogramming for their proliferation and effector functions when recruited to the tumor microenvironment (TME). However, the high metabolic activity of rapidly proliferating cancer cells can compete for nutrients with immune cells in the TME, and consequently, suppressing their anti-tumor functions. Thus, therapeutic strategies could aim to restore T cell metabolism and anti-tumor responses in the TME by targeting the metabolic dependence of cancer cells. In this review, we highlight current research progress on metabolic reprogramming and the interplay between cancer cells and immune cells. We also discuss potential therapeutic intervention strategies for targeting metabolic pathways to improve cancer immunotherapy efficacy.
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    An organoid-based screen for epigenetic inhibitors that stimulate antigen presentation and potentiate T-cell-mediated cytotoxicity
    (Springer Nature, 2021) Zhou, Zhuolong; Van der Jeught, Kevin; Fang, Yuanzhang; Yu, Tao; Li, Yujing; Ao, Zheng; Liu, Sheng; Zhang, Lu; Yang, Yang; Eyvani, Haniyeh; Cox, Mary L.; Wang, Xiyu; He, Xiaoming; Ji, Guang; Schneider, Bryan P.; Guo, Feng; Wan, Jun; Zhang, Xinna; Lu, Xiongbin; Medical and Molecular Genetics, School of Medicine
    In breast cancer, genetic heterogeneity, the lack of actionable targets and immune evasion all contribute to the limited clinical response rates to immune checkpoint blockade therapy. Here, we report a high-throughput screen based on the functional interaction of mouse- or patient-derived breast tumour organoids and tumour-specific cytotoxic T cells for the identification of epigenetic inhibitors that promote antigen presentation and potentiate T-cell-mediated cytotoxicity. We show that the epigenetic inhibitors GSK-LSD1, CUDC-101 and BML-210, identified by the screen, display antitumour activities in orthotopic mammary tumours in mice, that they upregulate antigen presentation mediated by the major histocompatibility complex class I on breast tumour cells and that treatment with BML-210 substantially sensitized breast tumours to the inhibitor of the checkpoint programmed death-1. Standardized measurements of tumour-cell killing activity facilitated by tumour-organoid-T-cell screens may help with the identification of candidate immunotherapeutics for a range of cancers.