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144 results on '"Zheng, Youshi"'

4. Multifunctional Biomimetic Nanocarriers for Dual‐Targeted Immuno‐Gene Therapy Against Hepatocellular Carcinoma.

Author

Sun, Yupeng, Liu, Yan, Li, Rui, Zhang, Cuilin, Wu, Ming, Zhang, Xiaolong, Zheng, Aixian, Liao, Naishun, Zheng, Youshi, Xu, Haipo, Zeng, Rui, Zeng, Yongyi, and Liu, Xiaolong

Subjects
IMMUNE checkpoint inhibitors, IMMUNOLOGIC memory, IMMUNE checkpoint proteins, IMMUNOLOGICAL adjuvants, CANCER relapse
Abstract

Growing evidences have proved that tumors evade recognition and attack by the immune system through immune escape mechanisms, and PDL1/Pbrm1 genes have a strong correlation with poor response or resistance to immune checkpoint blockade (ICB) therapy. Herein, a multifunctional biomimetic nanocarrier (siRNA‐CaP@PD1‐NVs) is developed, which can not only enhance the cytotoxic activity of immune cells by blocking PD1/PDL1 axis, but also reduce tumor immune escape via Pbrm1/PDL1 gene silencing, leading to a significant improvement in tumor immunosuppressive microenvironment. Consequently, the nanocarrier promotes DC cell maturation, enhances the infiltration and activity of CD8+ T cells, and forms long‐term immune memory, which can effectively inhibit tumor growth or even eliminate tumors, and prevent tumor recurrence and metastasis. Overall, this study presents a powerful strategy for co‐delivery of siRNA drugs, immune adjuvant, and immune checkpoint inhibitors, and holds great promise for improving the effectiveness and safety of current immunotherapy regimens. [ABSTRACT FROM AUTHOR]

Published
2024
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8. RNA methyltransferase FTSJ3 regulates the type I interferon pathway to promote hepatocellular carcinoma immune evasion

Author

Zhuang, Qiuyu, primary, Dai, Zhiguo, additional, Xu, Xuechun, additional, Bai, Shaoyi, additional, Zhang, Yindan, additional, Zheng, Youshi, additional, Xing, Xiaohua, additional, Hu, En, additional, Wang, Yingchao, additional, Guo, Wuhua, additional, Zhao, Bixing, additional, Zeng, Yongyi, additional, and Liu, Xiaolong, additional

Published
2023
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11. Navoximod modulates local HSV-1 replication to reshape tumor immune microenvironment for enhanced immunotherapy via an injectable hydrogel.

Author

Zhuang, Qiuyu, Zhao, Binyu, Lin, Zhiwen, Liang, Yuzhi, Zhao, Qingfu, Wang, Yunhao, Liao, Naishun, Tu, Haibin, Zheng, Youshi, Chen, Hengkai, Zeng, Yongyi, Zhang, Da, and Liu, Xiaolong

Subjects
MICE, HUMAN herpesvirus 1, TUMOR microenvironment, ONCOLYTIC virotherapy, IMMUNOTHERAPY
Abstract

Oncolytic virotherapy can lead to tumor lysis and systemic anti-tumor immunity, but the therapeutic potential in humans is limited due to the impaired virus replication and the insufficient ability to overcome the immunosuppressive tumor microenvironment (TME). To solve the above problems, we identified that Indoleamine 2, 3-dioxygenase 1 (IDO1) inhibitor Navoximod promoted herpes simplex virus type 1 (HSV-1) replication and HSV-1-mediated oncolysis in tumor cells, making it a promising combination modality with HSV-1-based virotherapy. Thus, we loaded HSV-1 and Navoximod together in an injectable and biocompatible hydrogel (V-Navo@gel) for hepatocellular carcinoma (HCC) virotherapy. The hydrogel formed a local delivery reservoir to maximize the viral replication and distribution at the tumor site with a single-dose injection. Notably, V-Navo@gel improved the disease-free survival time of HCC- bearing mice and protects the mice against tumor recurrence. What's more, V-Navo@gel also showed an effective therapeutic efficacy in the rabbit orthotopic liver cancer model. Mechanistically, we further discovered that our combination strategy entirely reprogramed the TME through single-cell RNA sequencing. All these results collectively indicated that the combination of Navoximod with HSV-1 could boost the viral replication and reshape TME for tumor eradication through the hydrogel reservoir. An injectable and biocompatible hydrogel loaded with both Indoleamine 2, 3-dioxygenase 1 (IDO1) inhibitor and herpes simplex virus type 1 (HSV-1) displays synergistic anti-cancer effects in vivo by remodeling the tumor microenvironment and generating immune memory effects. [ABSTRACT FROM AUTHOR]

Published
2023
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22. Cytosolic Delivery of Thiolated Neoantigen Nano‐Vaccine Combined with Immune Checkpoint Blockade to Boost Anti‐Cancer T Cell Immunity

Author

Zhang, Da, primary, Lin, Ziguo, additional, Wu, Ming, additional, Cai, Zhixiong, additional, Zheng, Youshi, additional, He, Lei, additional, Li, Zhenli, additional, Zhou, Jie, additional, Sun, Liqin, additional, Chen, Geng, additional, Zeng, Yongyi, additional, Li, Juan, additional, Liu, Jingfeng, additional, Yang, Huanghao, additional, and Liu, Xiaolong, additional

Published
2021
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31. HIF-1α and HDAC1 Mediated Down-Regulation of FAM99A Contributes to Hypoxia Induced HCC Metastasis

Author

Zhao, Bixing, primary, Ke, Kun, additional, Wang, Yingchao, additional, Wang, Fei, additional, Shi, Yingjun, additional, Li, Zhenli, additional, Zheng, Xiaoyuan, additional, Huang, Jingyun, additional, Liao, Naishun, additional, Cai, Zhixiong, additional, Lai, Yongping, additional, Zheng, Youshi, additional, Yang, Xiaoyu, additional, Liu, Xiaolong, additional, and Liu, Jingfeng, additional

Published
2020
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32. Inflammatory Micro-environment Contributes to Stemness Properties and Metastatic Potential of HCC via the NF-κB/miR-497/SALL4 Axis

Author

Zhao, Bixing, primary, Wang, Yingchao, additional, Tan, Xionghong, additional, Ke, Kun, additional, Zheng, Xiaoyuan, additional, Wang, Fei, additional, Lan, Shubing, additional, Liao, Naishun, additional, Cai, Zhixiong, additional, Shi, Yingjun, additional, Zheng, Youshi, additional, Lai, Yongping, additional, Wang, Lili, additional, Li, Qin, additional, Liu, Jingfeng, additional, Huang, Aimin, additional, and Liu, Xiaolong, additional

Published
2019
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34. Immunotherapy: Artificial Engineered Natural Killer Cells Combined with Antiheat Endurance as a Powerful Strategy for Enhancing Photothermal‐Immunotherapy Efficiency of Solid Tumors (Small 42/2019)

Author

Zhang, Da, primary, Zheng, Youshi, additional, Lin, Ziguo, additional, Lan, Shanyou, additional, Zhang, Xiaolong, additional, Zheng, Aixian, additional, Li, Juan, additional, Liu, Gang, additional, Yang, Huanghao, additional, Liu, Xiaolong, additional, and Liu, Jingfeng, additional

Published
2019
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35. Artificial Engineered Natural Killer Cells Combined with Antiheat Endurance as a Powerful Strategy for Enhancing Photothermal‐Immunotherapy Efficiency of Solid Tumors

Author

Zhang, Da, primary, Zheng, Youshi, additional, Lin, Ziguo, additional, Lan, Shanyou, additional, Zhang, Xiaolong, additional, Zheng, Aixian, additional, Li, Juan, additional, Liu, Gang, additional, Yang, Huanghao, additional, Liu, Xiaolong, additional, and Liu, Jingfeng, additional

Published
2019
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39. An Optogenetic Controllable T Cell System for Hepatocellular Carcinoma Immunotherapy

Author

Zhao, Bixing, primary, Wang, Yingchao, additional, Tan, Xionghong, additional, Zheng, Xiaoyuan, additional, Wang, Fei, additional, Ke, Kun, additional, Zhang, Cuilin, additional, Liao, Naishun, additional, Dang, Yuan, additional, Shi, Yingjun, additional, Zheng, Youshi, additional, Gao, Yunzhen, additional, Li, Qin, additional, Liu, Xiaolong, additional, and Liu, Jingfeng, additional

Published
2019
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40. Photoresponsive Nanovehicle for Two Independent Wavelength Light-Triggered Sequential Release of P-gp shRNA and Doxorubicin To Optimize and Enhance Synergistic Therapy of Multidrug-Resistant Cancer

Author

Wu, Ming, primary, Lin, Xinyi, additional, Tan, Xionghong, additional, Li, Jiong, additional, Wei, Zuwu, additional, Zhang, Da, additional, Zheng, Youshi, additional, Zheng, Ai-xian, additional, Zhao, Bixing, additional, Zeng, Yongyi, additional, Liu, Xiaolong, additional, and Liu, Jingfeng, additional

Published
2018
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49. The structural basis of the Tle4-Tli4 complex reveals the self-protection mechanism of H2-T6SS in Pseudomonas aeruginosa.

Author

Lu, Defen, Zheng, Youshi, Liao, Naishun, Wei, Ling, Xu, Bo, Liu, Xiaolong, and Liu, Jingfeng

Subjects
*PSEUDOMONAS aeruginosa, *SECRETION, *IMMUNITY, *COMPETITION (Biology), *CATALYTIC activity
Abstract

The type VI secretion system (T6SS) has recently been demonstrated to mediate interbacterial competition and to discriminate between self and nonself. T6SS+ bacteria employ toxic effectors to inhibit rival cells and concurrently use effector cognate immunity proteins to protect their sibling cells. The effector and immunity pairs (E-I pairs) endow the bacteria with a great advantage in niche competition. Tle4-Tli4 (PA1510-PA1509) is a newly identified E-I pair that is controlled by H2-T6SS in Pseudomonas aeruginosa. Tle4 exhibits phospholipase activity, which destroys the cell membrane of rival cells, and the periplasm-located Tli4 in donor cells eliminates this toxic effect of Tle4. In this paper, the structure of the Tle4-Tli4 complex is reported at 1.75 Å resolution. Tle4 consists of two domains: a conserved α/β-hydrolase domain and an unusual cap domain in which two lid regions (lid1 and lid2) display a closed conformation that buries the catalytic triad in a deep funnel. Tli4 also displays a two-domain structure, in which a large lobe and a small lobe form a crab claw-like conformation. Tli4 uses this crab claw to grasp the cap domain of Tle4, especially the lid2 region, which prevents the interfacial activation of Tle4 and thus causes enzymatic dysfunction of Tle4 in sister cells. [ABSTRACT FROM AUTHOR]

Published
2014
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50. RNA Methyltransferase FTSJ3 Regulates the Type I Interferon Pathway to Promote Hepatocellular Carcinoma Immune Evasion.

Author

Zhuang Q, Dai Z, Xu X, Bai S, Zhang Y, Zheng Y, Xing X, Hu E, Wang Y, Guo W, Zhao B, Zeng Y, and Liu X

Subjects
Animals, Humans, Mice, B7-H1 Antigen metabolism, Immune Checkpoint Inhibitors pharmacology, Immune Evasion, Immunotherapy, Methyltransferases genetics, RNA, Tumor Microenvironment, Carcinoma, Hepatocellular pathology, Interferon Type I pharmacology, Liver Neoplasms pathology
Abstract

Immunotherapies such as immune checkpoint blockade have achieved remarkable success in treating cancer. Unfortunately, response rates have been limited in multiple cancers including hepatocellular carcinoma (HCC). The critical function of epigenetics in tumor immune evasion and antitumor immunity supports harnessing epigenetic regulators as a potential strategy to enhance the efficacy of immunotherapy. Here, we discovered a tumor-promoting function of FTSJ3, an RNA 2'-O-methyltransferase, in HCC by suppressing antitumor immune responses. FTSJ3 was upregulated in hepatocellular carcinoma, and high FTSJ3 expression correlated with reduced patient survival. Deletion of FTSJ3 blocked HCC growth and induced robust antitumor immune responses. Mechanistically, FTSJ3 suppressed double-stranded RNA (dsRNA)-induced IFNβ signaling in a 2'-O-methyltransferase manner. Deletion of RNA sensors in HCC cells or systemic knockout of type I IFN receptor IFNAR in mice rescued the in vivo tumor growth defect caused by FTSJ3 deficiency, indicating that FTSJ3 deletion suppresses tumor growth by activating the RNA sensor-mediated type I IFN pathway. Furthermore, FTSJ3 deletion significantly enhanced the efficacy of programmed cell death protein 1 (PD-1) immune checkpoint blockade. The combination of FTSJ3 deficiency and anti-PD-1 antibody treatment effectively eradicated tumors and increased the survival time. In conclusion, this study reveals an epigenetic mechanism of tumor immune evasion and, importantly, suggests FTSJ3-targeting therapies as potential approach to overcome immunotherapy resistance in patients with HCC., Significance: Hepatocellular carcinoma cells use 2'-O-methylation catalyzed by FTSJ3 for immune evasion by suppressing abnormal dsRNA-mediated type I IFN responses, providing a potential target to activate antitumor immunity and enhance immunotherapy efficacy., (©2023 American Association for Cancer Research.)

Published
2024
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