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您的检索式：作者名="Lucy S.Cheng"
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| 1 | Enhancing the HSV-1-mediated antitumor immune response by suppressing Bach1显示文摘Background In 2015,herpes simplex virus 1(HSV-1)-derived talimogene laherparepvec(T-VEC)was the first oncolytic virus approved by the US Food and Drug Administration as a therapeutic agent for cancer treatment.However,its antitumor application is limited to local treatment of melanoma,and there is a lack of understanding of the mechanisms underlying the regulation of HSV-1 replication in cancer cells and the associated antitumor immunity.We hypothesized that increasing the replication capacity of HSV-1 in tumor cells would enhance the antitumor effect of this virus.Methods We systematically identified IFN-stimulated genes induced by HSV-1 by performing functional screens and clarified the mechanism by which BACH1 acts against HSV-1.Then,we tested the effect of BACH1 deficiency on immunogenic cell death induced by HSV-1.Furthermore,we investigated the antitumor effect of BACH1 deficiency on HSV-1 in MCA205 and B16 murine tumor models.Results We identified eight IFN-stimulated genes(ISGs)controlling HSV-1 replication,among which BTB and CNC homology 1(BACH1)suppressed HSV-1 replication by inhibiting the transcription of ICP4,ICP27,and UL39.Loss of Bach1 function not only increased HSV-1 proliferation but also promoted HSV-1-induced cell apoptosis,HMGB1 secretion,and calreticulin exposure in tumor cells.More importantly,hemin,an FDA-approved drug known to downregulate BACH1,significantly enhanced HSV-1-mediated antitumor activity with increased T lymphocyte infiltration at the tumor site.Conclusions Our studies uncovered a novel antiviral activity of BACH1 and provided a new strategy for improving the clinical efficiency of the oncolytic virus HSV-1. | Chaohu Pan Qiaomei Cai Xiaorong Li Lili Li Liping Yang Yu Chen Junxiao Liu Wancheng Liu Meiling Gao Tianqi Sui Xiaoyang Wang Huiming Fan Jiayin Ruan Yueyue Shi Saihua Chen Lucy S.Cheng Jiayong Liu Heng Yang Genhong Cheng | 2022 | Cellular & Molecular Immunology2022，19，4： | 0 |
| 2 | Homeoprotein SIX1 compromises antitumor immunity through TGF-β-mediated regulation of collagens显示文摘The tumor microenvironment(TME),including infiltrated immune cells,is known to play an important role in tumor growth;however,the mechanisms underlying tumor immunogenicity have not been fully elucidated.Here,we discovered an unexpected role for the transcription factor SIX1 in regulating the tumor immune microenvironment.Based on analyses of patient datasets,we found that SIX1 was upregulated in human tumor tissues and that its expression levels were negatively correlated with immune cell infiltration in the TME and the overall survival rates of cancer patients.Deletion of Six1 in cancer cells significantly reduced tumor growth in an immune-dependent manner with enhanced antitumor immunity in the TME.Mechanistically,SIX1 was required for the expression of multiple collagen genes via the TGFBR2-dependent Smad2/3 activation pathway,and collagen deposition in the TME hampered immune cell infiltration and activation.Thus,our study uncovers a crucial role for SIX1 in modulating tumor immunogenicity and provides proof-of-concept evidence for targeting SIX1 in cancer immunotherapy. | Wancheng Liu Meiling Gao Lili Li Yu Chen Huimin Fan Qiaomei Cai Yueyue Shi Chaohu Pan Junxiao Liu Lucy S.Cheng Heng Yang Genhong Cheng | 2021 | Cellular & Molecular Immunology2021，18，12： | 0 |
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