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Overcoming resistance to immunotherapy by targeting GPR84 in myeloid-derived suppressor cells

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Signal Transduction and Targeted Therapy 2023年第5期8卷 2408-2422页

作者： guohui qin Shasha Liu Jinyan Liu Hongwei Hu Li Yang Qitai Zhao Congcong Li Bin Zhang Yi Zhang Biotherapy Center and Cancer Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan450052China Department of Medicine-Division of Hematology/Oncology Feinberg School of Medicine Northwestern UniversityChicagoIL60611USA School of Life Sciences Zhengzhou UniversityZhengzhouHenan450001China Henan Key Laboratory for Tumor Immunology and Biotherapy ZhengzhouHenan450052China State Key Laboratory of Esophageal Cancer Prevention&Treatment Zhengzhou UniversityZhengzhouHenan450052China

Myeloid-derived suppressor cells(MDSCs)were found to gradually accumulate in the orthotopic esophageal cancer mouse model during tumor *** the roles of MDSCs in promoting tumor growth and inhibiting immune response have been extensively explored,currently,there are still no effective means for targeting MDSCs *** deficiency of specific markers of MDSCs was responsible for the limited strategy to eliminating in *** study identified that GPR84 was exclusively overexpressed on *** was further found that GPR84 was prominently expressed on MDSCs in clinical samples and tumor mouse models,which drives the immunosuppression on CD8^(+)T cells by inhibiting PD-L1 degradation in ***,G-CSF and GM-CSF were found to induce GPR84 expression through the STAT3/C/EBPβsignaling *** addition,GPR84+MDSCs and PD-L1^(+)MDSCs were highly accumulated in anti-PD-1 therapy-resistant patients with esophageal cancer,and high GPR84 signature risk was verified as a negative factor for the overall survival of patients with anti-PD-1 ***,GPR84 antagonism combined with an anti-PD-1 antibody enhanced the antitumor ***,targeting GPR84 enhanced anti-PD-1 efficacy in esophageal cancer and other malignant *** combination therapy has the potential for tumor therapy in clinics.

关键词： esophageal inhibiting suppressor

NEDD9 promotes cancer stemness by recruiting myeloid-derived suppressor cells via CXCL8 in esophageal squamous cell carcinoma

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Cancer Biology & Medicine 2021年第3期18卷 705-720页

作者： Dongli Yue Shasha Liu Tengfei Zhang Yong Wang guohui qin Xinfeng Chen Huanyu Zhang Dong Wang Lan Huang Feng Wang Liping Wang Song Zhao Yi Zhang Biotherapy Center the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Cancer Center the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of Etiology and Carcinogenesis and State Key Laboratory of Molecular Oncology National Cancer Center/Cancer HospitalChinese Academy of Medical Sciences(CAMS)&Peking Union Medical College(PUMC)Beijing 100730China Biomed Innovation Center Yehoo GroupShenzhen 518067China Department of Thoracic Surgery the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China School of Life Sciences Zhengzhou UniversityZhengzhou 450052China Henan Key Laboratory for Tumor Immunology and Biotherapy Zhengzhou 450052China

Objective:Esophageal squamous cell carcinoma(ESCC)has high morbidity and mortality rates *** stem cells(CSCs)may cause tumor initiation,metastasis,and recurrence and are also responsible for chemotherapy and radiotherapy ***-derived suppressor cells(MDSCs),in contrast,are known to be involved in mediating ***,we aimed to investigate the mechanisms of interaction of CSCs and MDSCs in the tumor ***:ESCC tissues and cell lines were *** precursor cell expressed,developmentally downregulated 9(NEDD9)was knocked down and overexpressed by lentiviral *** PCR,Western blot,immunohistochemistry,cell invasion,flow cytometry,cell sorting,multiplex chemokine profiling,and tumor growth analyses were ***:Microarray analysis revealed 10 upregulated genes in esophageal *** NEDD9 was upregulated in CSCs using the sphere-forming ***9 expression was correlated with tumor invasion(P=0.0218),differentiation(P=0.0153),and poor prognosis(P=0.0373).Additionally,NEDD9 was required to maintain the stem-like *** of chemokine expression in ESCC cells with NEDD9 overexpression and knockdown showed that NEDD9 regulated C-X-C motif chemokine ligand 8(CXCL8)expression via the ERK ***8 mediated the recruitment of MDSCs induced by NEDD9 in vitro and in *** promoted the stemness of ESCC cells through NEDD9 via the Notch ***:As a marker of ESCC,NEDD9 maintained the stemness of ESCC cells and regulated CXCL8 through the ERK pathway to recruit MDSCs into the tumor,suggesting NEDD9 as a therapeutic target and novel prognostic marker for ESCC.

关键词： Esophageal squamous cell carcinoma(ESCC) cancer stem cells(CSCs) neural precursor cell expressed,developmentally downregulated 9(NEDD9) myeloid derived suppressor cells(MDSCs)

Electrooxidative trifunctionalization of alkenes with N-chlorosuccinimide and ArSSAr/ArSH to α,β-dichloride arylsulfoxides

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Green Synthesis and Catalysis

Green Synthesis and Catalysis 2024年第2期5卷 131-135页

作者： guohui qin Renjie Wang Zhen Cheng Yonghong Zhang Bin Wang Yu Xia Weiwei Jin Chenjiang Liu Urumqi Key Laboratory of Green Catalysis and Synthesis Technology Key Laboratory of Oil and Gas Fine ChemicalsMinistry of Education&Xinjiang Uygur Autonomous RegionState Key Laboratory of Chemistry and Utilization of Carbon Based Energy ResourcesCollege of ChemistryXinjiang UniversityUrumqi 830017China

An unprecedented electrochemical oxidative trifunctionalization of olefins with diaryl disulfides/aryl thiols and N-chlorosuccinimide in an aqueous system is *** C-Cl bonds,one C-S bond,and one S=O bond are produced simultaneously in one step from simple and commercially available starting materials with clean *** tandem methodology features as mild reaction conditions,transition metal and additional oxidant free,broad substrate scope,good functional group compatibility,and gram scale preparation.

关键词： Electrooxidation Alkenes functionalization Vicinal dichlorination Sulfoxidation Tandem reaction

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髓源抑制性细胞的功能及其逆转策略

中国肿瘤生物治疗杂志 2020年第10期27卷 1073-1080页

作者：秦国慧张毅郑州大学第一附属医院生物细胞治疗中心河南郑州450052

髓源抑制性细胞(myeloid-derived suppressor cell,MDSC)是在骨髓中产生的一群具有高度异质性的免疫抑制细胞,在肿瘤等病理状态下大量聚集,是促进肿瘤进展、降低患者对传统治疗反应性的关键因素。近年来,免疫检查点阻断剂和基因工程T细... 详细信息

髓源抑制性细胞(myeloid-derived suppressor cell,MDSC)是在骨髓中产生的一群具有高度异质性的免疫抑制细胞,在肿瘤等病理状态下大量聚集,是促进肿瘤进展、降低患者对传统治疗反应性的关键因素。近年来,免疫检查点阻断剂和基因工程T细胞过继回输治疗延长了许多晚期恶性肿瘤患者的生存期,但上述免疫疗法在肺癌、结直肠癌等实体瘤中有效率仅为15%~40%,这与实体瘤免疫抑制微环境密切相关。MDSC在肿瘤微环境中聚集,通过抑制T细胞或NK细胞增殖及功能减弱宿主抗肿瘤免疫反应,是患者对免疫治疗耐受的关键机制。因此,明确MDSC聚集及功能特征是探索提高免疫治疗效果的重要研究方向。本文将系统阐述MDSC的产生、聚集及其免疫抑制功能的调控机制,概述目前靶向MDSC治疗的最新研究进展。

关键词：髓源抑制性细胞免疫抑制功能 MDSC产生与迁移肿瘤联合免疫治疗

基于三维图像的运动合理性判断方法研究与仿真

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现代电子技术 2017年第8期40卷 22-24页

作者：秦国辉保山学院云南保山678000

传统的运动合理性判断方法判断效率和判断准确度不高,为此,提出基于三维图像的运动合理性判断方法。利用三维图像人体运动模型采集人体运动数据,并以人体的新陈代谢速度和肌肉中乳酸含量为分类依据,对隐含运动损伤数据和人体合理运动数... 详细信息

传统的运动合理性判断方法判断效率和判断准确度不高,为此,提出基于三维图像的运动合理性判断方法。利用三维图像人体运动模型采集人体运动数据,并以人体的新陈代谢速度和肌肉中乳酸含量为分类依据,对隐含运动损伤数据和人体合理运动数据进行分类。分类结果经由人体状态特征解析函数,解析出分类结果中的人体状态是否合法。将解析出的合法数据输入到运动合理性判断仿真模型中,利用正逆向动力学确定人体结构参数、给出运动合理性判断结果。实验结果证明,所提方法的运动仿真误差较低、判断效率和判断准确度较高。

关键词：三维图像运动合理性判断运动数据采集仿真模型

基于Buck变换器的无刷直流电机无位置传感器控制

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电工技术学报 2017年第12期32卷 197-204页

作者：周闯秦国辉王玉鹏刘伟罗向东黑龙江省能源环境研究院哈尔滨150027

针对无位置传感器控制中换相时刻不准确及三相桥式逆变电路调压过程对前后级电路产生冲击的问题,提出一种基于Buck变换器的无刷直流电机无位置传感器控制方法。改用Buck变换器代替三相桥式逆变电路调压,有效削弱了PWM调制过程中高频谐... 详细信息

针对无位置传感器控制中换相时刻不准确及三相桥式逆变电路调压过程对前后级电路产生冲击的问题,提出一种基于Buck变换器的无刷直流电机无位置传感器控制方法。改用Buck变换器代替三相桥式逆变电路调压,有效削弱了PWM调制过程中高频谐波信号对前后级电路的冲击,线电压中高次谐波含量明显减少,母线电流及相电流波形更加平稳。设计的3次谐波滤波器滤波效果良好,且3次谐波电动势过零点易于检测。提出的90°-α相位补偿方式能够有效解决无位置传感器控制中换相时刻不准确的问题,并且可以明显减小感应电流对相电流产生的影响,使得相电流更加稳定。仿真和实验结果验证了该方法的可行性和有效性。

关键词： Buck变换器无位置传感器 3次谐波检测相位补偿

Decitabine enhances tumor recognition by T cells through upregulating the MAGE-A3 expression in esophageal carcinoma

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Decitabine enhances tumor recognition by T cells through upr...

髓细胞条件性METTL3基因敲除小鼠的构建与鉴定

第十三届全国免疫学学术大会

作者： Xiaojuan Shi Xinfeng Chen Baijun Fang Yu Ping guohui qin Dongli Yue Feng Li Shengli Yang Yi Zhang The First Affiliated Hospital of Zhengzhou University

Cancer testis(CT) antigens are expressed in various types of tumors and represent the potential targets for T cell-based immunotherapy. Analysis of CT gene expression and DNA methylation have indicated that certain CT genes are epigenetically regulated and studies have confirmed that certain CT antigens are regulated by DNA methylation. Here we explored the epigenetic regulation of MAGE-A3 and improved the clinical outcome of MAGE-A3-specific T cell therapy in esophageal squamous cell carcinoma(ESCC). We used molecular profiling datasets in The Cancer Genome Atlas(TCGA) to analyze CT gene expression in ESCC and its regulation by DNA methylation. We performed quantitative reverse transcription PCR(qRT-PCR), Immunohistochemistry(IHC) and bisulfite sequencing(BSP) in ESCC cell lines and ESCC tissues. We observed an efficient increase in MAGE-A3 expression in tumor cells and tissues after the treatment of decitabine(DAC), a clinical drug with demethylation function. Furthermore, we performed qRT-PCR in the peripheral blood mononuclear cells(PBMC) of myelodysplastic syndromes(MDS) patients. Functional assays, such as flow cytometry(FCM) and cytotoxicity assays, showed enhanced secretion of IFN-γ and cytolysis of MAGE-A3 antigen-specific T cells by DAC-treated target cells. In the tumor cell-xenograft mouse model and enzyme-linked immunospot(ELISPOT) assays, DAC increased the expression of MAGE-A3 and T cell mediated tumor clearance in ESCC as well. Notably, the proportions of MAGE-A3-responsive T cells were elevated in DAC-treated patients with MDS, indicating DAC dismissed the epigenetic inhibition of MAGE-A3. DAC would probably improve the clinical outcome of MAGE-A3-specific T cell therapy by augmenting the expression of target gene.

关键词： esophageal squamous cell carcinoma methylation antigen-specific T cell MAGE-A3 decitabine

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郑州大学学报（医学版） 2022年第4期57卷 509-514页

作者：陶佳嫦秦国慧李玲张毅郑州大学第一附属医院生物细胞治疗中心和肿瘤中心郑州450052

目的:构建髓细胞条件性METTL3基因敲除小鼠模型。方法:将Lyz2-cre^((+/+))雌性小鼠与METTL3^((flox/flox))雄性小鼠杂交,得到METTL3^((flox/-))Lyz2-cre^((+/-))杂合子小鼠,该杂合子小鼠自交,得到METTL3^((flox/flox))Lyz2-cre^((+/+))小鼠。提取小鼠鼠尾组织DNA,经PCR扩增、琼脂糖凝胶电泳和DNA序列测定,在DNA水平判断小鼠基因型;提取小鼠骨髓细胞RNA,利用RT-PCR法检验METTL3的敲除效率;利用成像流式细胞仪在蛋白水平分析髓细胞中METTL3的敲除效率。结果与结论:在DNA、RNA和蛋白水平分别验证了髓细胞条件性METTL3基因敲除小鼠模型构建成功,该小鼠存活并且可育,为研究METTL3在髓源抑制性细胞功能中的作用提供了研究平台。

关键词： METTL3基因基因敲除小鼠 cre/loxp小鼠髓源抑制性细胞

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对CBA人员国际交流的研究

安徽体育科技 2008年第6期29卷 10-13页

作者：秦国辉张璠保山师专体育系云南保山678000 新乡学院体育系河南新乡453003

通过文献资料法、访谈法和数理统计法,对CBA人员的国际交流情况进行研究,结果显示:CBA在运动员的引进来与走出去之间显得极不平衡,目前出国打球的球员仅有2名;13年来引进外援的数量总体呈上升趋势,但外援的选秀范围比较小,集中在美国;1... 详细信息

通过文献资料法、访谈法和数理统计法,对CBA人员的国际交流情况进行研究,结果显示:CBA在运动员的引进来与走出去之间显得极不平衡,目前出国打球的球员仅有2名;13年来引进外援的数量总体呈上升趋势,但外援的选秀范围比较小,集中在美国;13年来,共计有29名外籍教练员在CBA球队中担任过教练员,其中美国教练员占绝对的优势,存在着外教执教时间短和执教空间被压缩的问题。

关键词： CBA 人员国际交流