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Exhaustion and senescence: two crucial dysfunctional states of T cells in the tumor microenvironment

Cellular & Molecular Immunology 2020年第1期17卷 27-35页

作者： Yangjing Zhao Qixiang Shao guangyong peng Division of Infectious Diseases Allergy&Immunology and Department of Internal MedicineSaint Louis University School of MedicineSaint LouisMO 63104USA Department of Immunology Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu ProvinceSchool of MedicineJiangsu UniversityZhenjiang 212013P.R.China Department of Molecular Microbiology&Immunology Saint Louis University School of MedicineSt.LouisMO 63104USA

The failure of a massive influx of tumor-infiltrating T lymphocytes to eradicate tumor cells in the tumor microenvironment is mainly due to the dysfunction of T cells hyporesponsive to tumors.T-cell exhaustion and senescence induced by malignant tumors are two important dysfunctional states that coexist in cancer patients,hindering effective antitumor immunity and immunotherapy and sustaining the suppressive tumor *** exhausted and senescent T cells share a similar dysfunctional role in antitumor immunity,they are distinctly different in terms of generation,development,and metabolic and molecular regulation during tumor ***,we discuss the unique phenotypic and functional characteristics of these two types of dysfunctional T cells and their roles in tumor development and *** addition,we further discuss the potential molecular and metabolic signaling pathways responsible for the control of T-cell exhaustion and senescence in the suppressive tumor *** these critical and fundamental features should facilitate rethinking the unresponsiveness to current immunotherapies in clinical patients and lead to further development of novel and effective strategies that target different types of dysfunctional T cells to enhance cancer immunotherapy.

关键词： T-cell dysfunction Exhaustion Senescence Tumor microenvironment Inhibitory receptor Metabolism Checkpoint blockade

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TLR-mediated metabolic reprogramming in the tumor microenvironment: potential novel strategies for cancer immunotherapy

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Cellular & Molecular Immunology 2018年第5期15卷 1-10页

作者： Lan Huang Huaxi Xu guangyong peng Division of Infectious Diseases Allergy and ImmunologyDepartment of Internal MedicineSaint Louis University School of MedicineSaint LouisMO 63104USA Department of Microbiology and Immunology Jiangsu University School of MedicineZhenjiang 212013China Correspondence:G PengMDPhDDivision of Infectious DiseasesAllergy and ImmunologyDepartment of Internal MedicineSaint Louis University School of MedicineSaint LouisMO 63104USA.

Cellular energy metabolism not only promotes tumor cell growth and metastasis but also directs immune cell survival,proliferation and the ability to perform specific and functional immune responses within the tumor microenvironment.A better understanding of the molecular regulation of metabolism in different cell components in the tumor-suppressive microenvironment is critical for the development of effective strategies for human cancer ***-like receptors(TLRs)have recently been recognized as critical factors involved in tumor pathogenesis,regulating both tumor cells and tumor-infiltrating innate and adaptive immune ***,little is known about the molecular crosstalk between TLR signaling and tumor or/and immune cell metabolism,although there is abundant expression of TLRs in these *** this review,we explore the functional role of TLR signaling in reprogramming cell metabolism in the tumor *** particular,we discuss how malignant tumors regulate metabolism to support their growth and survival,summarize more recently identified metabolic profiles of different immune cell subsets and TLR-mediated regulation of cellular metabolism in both tumor and immune cells,and further explore potential strategies targeting cell metabolism for TLR-based cancer *** improved understanding of these issues should open new avenues for the development of novel strategies via TLR-mediated metabolic reprogramming of the tumor microenvironment for cancer immunotherapy.

关键词： checkpoint blockade immunotherapy metabolic reprogramming tumor microenvironment warburg effect

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Author Correction:A novel recombinant DNA vaccine encoding Mycobacterium tuberculosis ESAT-6 and FL protects against Mycobacterium tuberculosis challenge in mice

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The Journal of Biomedical Research 2022年第6期36卷 448-450页

作者： Qingtao Jiang Jing Zhang Xia Chen Mei Xia Yanlai Lu Wen Qiu Ganzhu Feng Dan Zhao Yan Li Fengxia He guangyong peng Yingwei Wang Department of Microbiology and Immunology Nanjing Medical UniversityNanjingJiangsu 211166China Division of Infectious Diseases Allergy and ImmunologyDepartment of Internal MedicineSaint Louis University School of MedicineSt.LouisMissouri 63104USA

Correction to:Journal of Biomedical Research https://***/10.7555/JBR.27.20120114,published on 30 September *** apologize for the misused images in Fig.7 in our article published on 30 September *** Fig.7 by HE staining and immunohistochemistry were partially misused because of our *** we couldn't find the original pictures acquired 11 years ago,thus HE and IHC experiments were repeated by our previously reserved wax ***,the pictures taken by microscope imaging system in each group were collected and combined,*** correct version of Fig.

关键词： tuberculosis immunohistochemistry picture

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Pilot Study of Ultrafiltration-Nanofiltration Process for the Treatment of Raw Water from Huangpu River in China

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Journal of Water Resource and Protection 2009年第3期1卷 203-209页

作者： Jianping ZHOU Naiyun GAO guangyong peng Yang DENG 不详

Pilot-scale test was carried out to evaluate the performance of a combined ultrafiltration (UF)-nanofiltration (NF) membrane process for the treatment of raw water from Huangpu River, Shanghai, in China. Results showed that UF could significantly remove turbidity, iron and manganese, and also could retain a part of high molecular weight (MW) organic compounds. Subsequently, NF could further reject low MW organics and inorganic salts, and ensured the treated water to reach the Standards for Drinking Water Quality in China. It seemed that 90 L/m2·h was an appropriate permeate flux for UF system when the raw water was directly filtered by UF membrane, the addition of coagulant (alum or ferric chloride) was not preferable to mitigate the fouling of the UF membrane. After near 120 days operation, the permeate flux of NF could be main-tained at 24-25 L/m2·h steadily, and no chemical clean was required.

关键词： Ultrafiltration Nanofiltration Permeate Flux Fouling

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A novel recombinant DNA vaccine encodingMycobacterium tuberculosis ESAT-6 and FL protects againstMycobacterium tuberculosis challenge in mice

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The Journal of Biomedical Research 2013年第5期27卷 406-420页

作者： Qingtao Jiang Jing Zhang Xia Chen Mei Xia Yanlai Lu Wen Qiu Ganzhu Feng Dan Zhao Yan Li Fengxia He guangyong peng Yingwei Wang Department of Microbiology and Immunology Nanjing Medical University Division of Infectious Diseases Allergy and Immunology Department of Internal MedicineSaint Louis University School of Medicine

Mycobacterium tuberculosis 6-kDa early secretory antigenic target （ESAT-6） is a dominant target antigen for cell-mediated immunity in the early phase of tuberculosis. The fms-like tyrosine kinase 3 ligand （FL） that induces potent immune response has been used as an adjuvant in vaccine development. In this study, a new recombinant plasmid （plRES-epitope-peptides-FL） encoding three T cell epitopes of ESAT-6 and FL was constructed, and the immunogenicity of the DNA vaccine was assessed in C57BL/6 mice immunized with the plasmid DNA vaccine. Additionally, a strategy of intramuscular injection with the DNA vaccine （prime） and intranasal administration of the epitope peptides （boost） was employed to induce higher immune reaction of the mice. The results showed that mice vaccinated with the recombinant plasmid DNA vaccine and boosted with the peptides not only increased the levels of Thl cytokines （IFN-γ and IL-12）, the number of IFN-γ＋ T cells and activities of cytotoxic T lymphocytes as well as IgG, but also enhanced protection against Mycobacterium tuberculosis challenge. In conclusion, these data indicate that the novel recombinant plRES-epitope-peptides-FL plasmid is a useful DNA vaccine for pre- venting Mycobacterium tuberculosis infection.

关键词： early secretory antigenic target-6 (ESAT-6) fms-like tyrosine kinase 3 ligand (FL) Mycobacteriumtuberculosis recombinant plasmid T cell epitopes

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长江下游城市应急供水水源工程设计与水质保障措施

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净水技术 2017年第7期36卷 87-90,95页

作者：彭广勇上海城建市政工程(集团)有限公司上海200065

为解决长江下游城市面临水质下降和突发污染等风险,诸多城市已开展应急供水水源的规划与建设,但如何保障已建应急供水水源的水质安全是各水源地管理单位普遍遇到的难题。以南通应急供水水源地星湖和云湖为例,介绍水源地建设规模和工程... 详细信息

为解决长江下游城市面临水质下降和突发污染等风险,诸多城市已开展应急供水水源的规划与建设,但如何保障已建应急供水水源的水质安全是各水源地管理单位普遍遇到的难题。以南通应急供水水源地星湖和云湖为例,介绍水源地建设规模和工程设计中采取的水质安全保障措施。经过运行实践证明,在工程设计时采取适当的工程措施,在运行时加以勤换水、合理投放水生动植物等的管理措施,可以有效保障应急供水水源地水质安全。总结提炼的相关经验可供相似城市参考借鉴。

关键词：应急供水水源平原型水库水质安全保障工程设计运行经验长江下游

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考虑粉细砂应变软化特性的修正双曲线模型

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四川轻化工大学学报（自然科学版） 2024年第3期37卷 94-100页

作者：许宇浩彭世龙曹广勇张挺安徽建筑大学土木工程学院合肥230601 建筑结构与地下工程安徽省重点实验室合肥230601

在基础建设过程中,以粉细砂为填筑材料的地基在上覆荷载作用下可能发生软化现象。为探究饱和粉细砂应变软化规律,基于自动环境三轴试验系统开展合肥粉细砂固结不排水三轴剪切试验,分析不同围压下粉细砂应变软化特征,揭示其软化机理。研... 详细信息

在基础建设过程中,以粉细砂为填筑材料的地基在上覆荷载作用下可能发生软化现象。为探究饱和粉细砂应变软化规律,基于自动环境三轴试验系统开展合肥粉细砂固结不排水三轴剪切试验,分析不同围压下粉细砂应变软化特征,揭示其软化机理。研究结果表明:合肥粉细砂不排水剪切应力-应变曲线呈明显驼峰型软化特征;围压对于其应力-应变曲线影响显著,其峰值偏差应力及对应的峰值应变与固结围压呈正相关,偏差应力峰值与固结围压关系可用线性函数(σ1-σ3)p=0.637σ3+255.5拟合表述,拟合决定系数R2达到0.983,应变峰值与固结围压关系可用线性函数εp=0.0031σ3+5.45拟合表述,拟合决定系数R2达到0.982;剪切过程粉细砂试样产生剪胀现象,使得土体结构逐渐破坏,进而发生应变软化现象。通过在沈珠江院士提出的驼峰形双曲线型公式上添加新的边界条件以简化模型参数,构建了合肥粉细砂应变软化修正双曲线数学模型。该模型对合肥粉细砂应力-应变软化曲线的拟合效果良好,为安徽地区地下工程设计与施工提供重要依据。

关键词：粉细砂三轴试验应变软化非线性力学模型应力-应变关系曲线

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Development of human herpesvirus-6-specific regulatory T cells

Development of human herpesvirus-6-specific regulatory T cel...

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第九届全国免疫学学术大会

作者： Fang Wang Jing Chi guangyong peng Feng Zhou Jinfeng Wang Lingyun Li Dongju Feng Fangyi Xie Bin Gu Jian Qin Yun Chen Kun Yao Department of Laboratory Medicine the First Affiliated Hospital of Nanjing Medical University Department of Microbiology and Immunology Nanjing Medical University Division of Infectious Diseases Allergy & Immunology and Department of Internal MedicineSaint Louis UniversitySt.LouisMissouri 63104 Department of Developmental Genetics Nanjing Medical University College of Foreign Languages Hehai University

Background:Human herpesvirus 6(HHV-6)is an important immunosuppressive and immunomodulatory *** mechanisms by which HHV-6 establishes latency and immunosuppression in its host are not well ***:HHV-6-specific

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A Comparative Study on Effects of the Infectionswith HHV-6Nanjing Local Strain CN5 and Standard Strain GSon CD Antigen Expressionof Cord Blood Mononuclear Cells in vitro

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The Journal of Biomedical Research 2000年第1期14卷 19-23页

作者： Ji Xiaohui(季晓辉) peng guangyong(彭光勇) Yao Kun(姚 ) Zhao Bei(赵蓓) Ren Qiang(任强) Zhou Yaoxi(周瑶玺) Department of Microbiology and Immunology, Nanjing Medical University, Nanjing 210029, P.R.China Department of Microbiology and Immunology Nanjing Medical UniversityNanjing 210029P. R. China

Objective\ To investigate the effects of HHV 6 infection on the expression of CD antigen and the difference between GS strain and CN\-5 strain. Methods\ The study was performed in vitro by using cord blood mononuclear cells (CBMCs) and inoculating them with the local strain CN\-5 or GS strain of HHV 6 and then practicing APAAP staining for CD antigen expressions. Results\ ①Both infections of GS strain and CN\-5 strain inhibited CD\-3 expressions and the inhibitory effect of GS infection was more remarkable, while neither GS nor CN\-5 infection induced the change of CD\-2 expression. ②CD\-4 positive cell percentage increased not only in the cells infected with GS strain, but also in those with CN\-5 strain, while CD\-8 positive cell percentage decreased only in the cells infected with GS strain, not in those with CN\-5 strain; so the ratio of CD\-4 to CD\-8 rose significantly in the cells infected with GS strain. ③ The percentages of CD\-\{45\}RA positive cells dropped with the infection of GS but not with that of CN\-5. Conclusion\ HHV 6 infection could disturb the expressions of some kinds of CD antigens in mononuclear cells and this disturbance could be induced by GS strain of type A more obvious than that by CN\-5 strain of type B.\;

关键词： HHV 6 CD antigen

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Pilot Study of Ultrafiltration-Nanofiltration Process for the Treatment of Raw Water from Huangpu River in China

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Journal of Water Resource and Protection 2009年第3期

作者： Jianping ZHOU Naiyun GAO guangyong peng Yang DENG

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