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Single-cell atlas reveals a distinct immune profile fostered by T cell-B cell crosstalk in triple negative breast cancer

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Cancer Communications 2023年第6期43卷 661-684页

作者： Shuning Ding niu qiao Qingchen Zhu Yiwei Tong Shengyue Wang Xiaosong Chen Qiang Tian Yichuan Xiao Kunwei Shen Department of General Surgery Comprehensive Breast Health CenterRuijin HospitalShanghai Jiao Tong University School of MedicineShanghaiP.R.China Shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine at ShanghaiRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiP.R.China Chinese Academy of Sciences Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and HealthChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghaiP.R.China

Background:Characterizing the unique immune microenvironment of each tumor is of great importance for better predicting prognosis and guiding cancer ***,the unique features of the immune microenvironment of triple negative breast cancer(TNBC)compared with other subtypes of breast cancer remain ***,we aimed to depict and compare the immune landscape among TNBC,human epidermal growth factor receptor 2-positive(HER2^(+))breast cancer,and luminal-like breast ***:Single-cell RNA sequencing(scRNA-seq)was performed on CD45^(+)immune cells isolated from human normal breast tissues and primary breast tumors of various *** analyzing the scRNA-seq data,immune cell clusters were identified and their proportions as well as transcriptome features were compared among TNBC,human HER2^(+)breast cancer,and luminal-like breast *** and cell-cell communication analyses were also conducted to characterize the immune ***:ScRNA-seq data of 117,958 immune cells were obtained and 31 immune clusters were identified.A unique immunosuppressive microenvironment in TNBC was decoded as compared to that in HER2^(+)or luminal-like breast cancer,which was characterized by higher proportions of regulatory T cells(Tregs)and exhausted CD8+T cells and accompanied by more abundant plasma *** and exhausted CD8+T cells in TNBC exhibited increased immunosuppression signature and dysfunctional *** analyses showed that B cells tended to differentiate to plasma cells in ***-cell communication analyses indicated that these unique features are fostered by the diversified T cell-B cell crosstalk in *** on the T cell-B cell crosstalk,a prognostic signaturewas established that could effectively predict the prognosis status for patients with ***,it was found that TNBC had a higher proportion of cytotoxic natural killer(NK)cells,whereas HER2^(+)or luminal-like breast cancer lost this f

关键词： breast cancer prognostic signature single-cell RNA sequencing T cell-B cell crosstalk triplenegative breast cancer tumor immune microenvironment

Early assessment of the safety and immunogenicity of a third dose(booster)of COVID-19 immunization in Chinese adults

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Frontiers of Medicine 2022年第1期16卷 93-101页

作者： Yuntao Zhang Yunkai Yang niu qiao Xuewei Wang Ling Ding Xiujuan Zhu Yu Liang Zibo Han Feng Liu Xinxin Zhang Xiaoming Yang China National Biotec Group Company Limited Beijing 100024China Shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine at ShanghaiRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China Beijing Institute of Biological Products China National Biotec Group Company LimitedBeijing 100176China National Vaccine and Serum Institute China National Biotec Group Company LimitedBeijing 101111China Department of Infectious Diseases Research Laboratory of Clinical VirologyRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China

Inducing durable and effective immunity against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)via vaccination is essential to combat the current pandemic of coronavirus disease 2019(COVID-19).It has been noticed that the strength of anti-COVID-19 vaccination-induced immunity fades over time,which calls for an additional vaccination regime,as known as booster immunization,to restore immunity among previously vaccinated *** we report a pilot open-label trial of a third dose of BBIBP-CorV,an inactivated SARS-CoV-2 vaccine(Vero cell),on 136 participants aged between 18 to 63 *** and immunogenicity in terms of neutralizing antibody titers and cytokine/chemokine responses were analyzed as the main endpoint until day *** systemic reactogenicity was either absent or mild,SARS-CoV-2-specific neutralizing antibody titers rapidly arose in all participants within 4 weeks,surpassing the peak antibody titers elicited by the initial two-dose immunization *** increases of cellular immunity-associated cytokines and chemokines were also detected in the majority of participants after the third ***,in an exploratory study,a newly developed recombinant protein vaccine,NVSI-06-08(CHO Cells),was found to be safe and even more effective than BBIBP-CorV in eliciting humoral immune responses in BBIBP-CorV-primed ***,these results indicate that a third immunization schedule with either homologous or heterologous vaccine showed favorable safety profiles and restored potent SARS-CoV-2-specific immunity,providing support for further trials of booster vaccination in larger populations.

关键词： COVID-19 SARS-CoV-2 vaccine immunization booster immunization

Cross-sectional network analysis of plasma proteins/metabolites correlated with pathogenesis and therapeutic response in acute promyelocytic leukemia

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Frontiers of Medicine 2024年第2期18卷 327-343页

作者： niu qiao Yizhu Lyu Feng Liu Yuliang Zhang Xiaolin Ma Xiaojing Lin Junyu Wang Yinyin Xie Ruihong Zhang Jing qiao Hongming Zhu Li Chen Hai Fang Tong Yin Zhu Chen Qiang Tian Saijuan Chen Shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine at ShanghaiRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200025China Department of Hematology Second Hospital of Dalian Medical UniversityDalian116021China

The treatment of PML/RARA+acute promyelocytic leukemia(APL)with all-trans-retinoic acid and arsenic trioxide(ATRA/ATO)has been recognized as a model for translational medicine *** an altered microenvironment is a general cancer hallmark,how APL blasts shape their plasma composition is poorly ***,we reported a cross-sectional correlation network to interpret multilayered datasets on clinical parameters,proteomes,and metabolomes of paired plasma samples from patients with APL before or after ATRA/ATO induction *** study revealed the two prominent features of the APL plasma,suggesting a possible involvement of APL blasts in modulating plasma *** was characterized by altered secretory protein and metabolite profiles correlating with heightened proliferation and energy consumption in APL blasts,and the other featured APL plasma-enriched proteins or enzymes catalyzing plasma-altered metabolites that were potential trans-regulatory targets of PML/***,results indicated heightened interferon-gamma signaling characterizing a tumor-suppressing function of the immune system at the first hematological complete remission stage,which likely resulted from therapy-induced cell death or senescence and ensuing supraphysiological levels of intracellular ***,our work sheds new light on the pathophysiology and treatment of APL and provides an information-rich reference data cohort for the exploratory and translational study of leukemia microenvironment.

关键词： acute promyelocytic leukemia plasma proteomics plasma metabolomics cross-sectional correlation network pathogenesis treatment

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铝致神经细胞死亡的研究进展

中华劳动卫生职业病杂志 2010年第3期28卷 226-227页

作者：牛侨山西医科大学公共卫生学院太原030001

正常情况下，铝在生物体内的含量很少。但由于近代铝矿的开采以及炼铝工业的发展、铝制品的制作加工使用、酸雨的频繁发生溶解硅铝酸盐进入河流和湖泊、食品添加剂的广泛使用等，铝以各种形式通过呼吸道、消化道等多种途径进入人体，人... 详细信息

正常情况下，铝在生物体内的含量很少。但由于近代铝矿的开采以及炼铝工业的发展、铝制品的制作加工使用、酸雨的频繁发生溶解硅铝酸盐进入河流和湖泊、食品添加剂的广泛使用等，铝以各种形式通过呼吸道、消化道等多种途径进入人体，人群机体内铝负荷越来越高。研究发现，进入机体的铝以Al（H2O）^3＋的形式与转铁蛋白、白蛋白或枸橼酸离子相结合，随血液分布于哺、肝、肾、骨、肺等组织中。

关键词：神经细胞死亡炼铝食品添加剂生物体内转铁蛋白机体内铝制品溶解硅

探究环境因素损害神经机制,尝试预防性干预措施

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环境与职业医学 2023年第3期40卷 237-238页

作者：牛侨山西医科大学公共卫生学院山西太原030001

神经系统是人体最重要的系统,越来越多神经毒性化学物作用于神经系统,造成认知功能损害。本文对环境因素的神经毒作用及与神经退行性疾病的关系做了扼要介绍。针对常见的金属铝、锰、铁对神经系统的损害,本专栏尝试了较为客观的影像学... 详细信息

神经系统是人体最重要的系统,越来越多神经毒性化学物作用于神经系统,造成认知功能损害。本文对环境因素的神经毒作用及与神经退行性疾病的关系做了扼要介绍。针对常见的金属铝、锰、铁对神经系统的损害,本专栏尝试了较为客观的影像学指标和认知量表相结合评价损害程度,用体外实验探讨了毒作用机制,包括调控多巴胺神经递质分泌、tau蛋白过度磷酸化。专栏文章还针对电离辐射对神经系统的损害,尝试用富氢水干预并阐述了干预机制是调控磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)/半胱氨酸天冬氨酸特异性蛋白酶9(Caspase-9)通路、Toll样受体4(TLR4)/核因子-κB(NF-κB)信号通路。

关键词：环境因素神经系统毒作用机制干预措施

The RAS/PI3K Pathway is Involved in the Impairment of Long-term Potentiation Induced by Acute Aluminum Treatment in Rats

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Biomedical and Environmental Sciences 2016年第11期29卷 782-789页

作者： SONG Jing LIU Ying ZHANG Hui Fang niu qiao Department of Occupational Health School of Public HealthShanxi Medical University

Objective To explore the role of RAS/PI3K pathway in the impairment of long-term potentiation （LTP） induced by acute aluminum （AI） treatment in rats in vivo. Methods First, different dosages of aluminum-maltolate complex [Al（mal）3] were given to rats via acute intracerebroventricular （i.c.v.） injection. Following AI exposure, the RAS activity of rat hippocampus were detected by ELISA assay after the hippocampal LTP recording by field potentiation technique in vivo. Second, the antagonism on the aluminum-induced suppression of hippocampal LTP was observed after the treatment of the RAS activator epidermal growth factor （EGF）. Finally, the antagonism on the downstream molecules （PKB activity and the phosphorylation of GluR1 $831 and $845） were tested by ELISA and West-blot assays at the same time. Results With the increasing aluminum dosage, a gradually decreasing in RAS activity of the rat hippocampus was produced after a gradually suppressing on LTP. The aluminum-induced early suppression of hippocampal LTP was antagonized by the RAS activator epidermal growth factor （EGF）. And the EGF treatment produced changes similar to those observed for LTP between the groups on PKB activity as well as the phosphorylation of GluR1 S831 and s845. Conclusion The RAS-PI3K/PKB-GluR1 S831 and S845 signal transduction pathway may be involved in the inhibition of hippocampal LTP by aluminum exposure in rats. However, the mechanisms underlying this observation need further investigation.

关键词： Aluminum Long-term potentiation RAS PKB AMPA receptor

Effects of Exposure to Aluminum on Long-term Potentiation and AMPA Receptor Subunits in Rats in vivo

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Biomedical and Environmental Sciences 2014年第2期27卷 77-84页

作者： SONG Jing LIU Ying ZHANG Hui Fang ZHANG Qin Li niu qiao Department of Occupational Health School of Public Health Shanxi Medical University

Objective To explore the effects of exposure to aluminum （AI） on long-term potentiation （LTP） and AMPA receptor subunits in rats in vivo. Methods Different dosages of aluminum-maltolate complex [Al（mal）3] were given to rats via acute intracerebroventricular （i.c.v.） injection and subchronic intraperitoneal （i.p.） injection. Following AI exposure, the hippocampal LTP were recorded by field potentiation technique in vivo and the expression of AMPAR subunit proteins （GluR1 and GluR2） in both total and membrane-enriched extracts from the CA1 area of rat hippocampus were detected by Western blot assay. Results Acute AI treatment produced dose-dependent suppression of LTP in the rat hippocampus and dose-dependent decreases of GluRz and GluR2 in membrane extracts; however, no similar changes were found in the total cell extracts, which suggests decreased trafficking of AMPA receptor subunits from intracellular pools to synaptic sites in the hippocampus. The dose-dependent suppressive effects on LTP and the expression of AMPA receptor subunits both in the membrane and in total extracts were found after subchronic AI treatment, indicating a decrease in AMPA receptor subunit trafficking from intracellular pools to synaptic sites and an additional reduction in the expression of the subunits. Conclusion Al（mal）3 obviously and dose-dependently suppressed LTP in the rat hippocampal CA1 region in vivo, and this suppression may be related to both trafficking and decreases in the expression of AMPA receptor subunit proteins. However, the mechanisms underlying these observations need further investigation.

关键词： Aluminum-maltolate complex Long-term potentiation AMPA receptor Hippocampus invivo

Impact of Sub-chronic Aluminium-maltolate Exposure on Catabolism of Amyloid Precursor Protein in Rats

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Biomedical and Environmental Sciences 2013年第6期26卷 445-452页

作者： LIANG Rui Feng LI Wei Qing WANG Hong WANG Jun Xia niu qiao Department of Occupational Health School of Public HealthShanxi Medical University Department of Environmental Health School of Public HealthShanxi Medical University

Objective To investigate the impact of sub-chronic Aluminium-maltolate [Al（mal）s] exposure on the catabolism of amyloid precursor protein （APP） in rats. Methods Forty adult male Sprague-Dawley （SD） rats were randomly divided into five groups： the control group, the maltolate group （7.56 mg/kg BW）, and the Al（mal）s groups （0.27, 0.54, and 1.08 mg/kg BW, respectively）. Control rats were administered with 0.9% normal saline through intraperitoneal （i.p.） injection. Maltolate and Al（mal）s were administered to the rats also through i.p. injections. Administration was conducted daily for two months. Rat neural behavior was examined using open field tests （OFT）. And the protein expressions and their mRNAs transcription related with APP catabolism were studied using enzyme-linked immunosorbent assay （ELISA） and real-time polymerase chain reaction （RT-PCR）. Results The expressions of APP, 13-site APP cleaving enzyme 1 （BACEI） and presenilin-1 （PSi） proteins and their mRNAs transcription increased gradually with the increase of Al（mal）3 doses （P〈0.05）. The enzyme activity of BACEI in the 0.54 and 1.08 mg/kg Al（mal）s groups increased significantly （P〈0.05）. The expression of 8-amyloid protein （AS） 1-40 gradually decreased while the protein expression of A81-42 increased gradually with the increase of Al（mal）s doses （P〈0.05）. Conclusion Result from our study suggested that one of the possible mechanisms that Al（mal）s can cause neurotoxicity is that Al（mal）s can increase the generation of A81-42 by facilitating the expressions of APP, β-, and γ-secretase.

关键词： Aluminium-maltolate Amyloid precursor protein 6-amyloid protein Rat

Immunosuppressive tumor microenvironment contributes to tumor progression in diffuse large B-cell lymphoma upon anti-CD19 chimeric antigen receptor T therapy

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Frontiers of Medicine 2023年第4期17卷 699-713页

作者： Zixun Yan Li Li Di Fu Wen Wu niu qiao Yaohui Huang Lu Jiang Depei Wu Yu Hu Huilai Zhang Pengpeng Xu Shu Cheng Li Wang Sahin Lacin Muharrem Muftuoglu Weili Zhao Shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine at ShanghaiRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China Institute of Hematology The First Affiliated Hospital of Soochow UniversitySuzhou 215000China Institute of Hematology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430000China Tianjin Medical University Cancer Institute&Hospital Tianjin 300070China University of Texas MD Anderson Cancer Center HoustonTexas 77030USA Laboratory of Molecular Pathology Pôle de Recherches Sino-Français en Science du Vivant et GénomiqueShanghai 200025China

Anti-CD19 chimeric antigen receptor(CAR)-T cell therapy has achieved 40%–50%long-term complete response in relapsed or refractory diffuse large B-cell lymphoma(DLBCL)***,the underlying mechanism of alterations in the tumor microenvironments resulting in CAR-T cell therapy failure needs further investigation.A multi-center phase I/II trial of anti-CD19 CD28z CAR-T(FKC876,ChiCTR1800019661)was *** 22 evaluable DLBCL patients,seven achieved complete remission,10 experienced partial remissions,while four had stable disease by day ***-cell RNA sequencing results were obtained from core needle biopsy tumor samples collected from long-term complete remission and early-progressed patients,and compared at different stages of treatment.M2-subtype macrophages were significantly involved in both in vivo and in vitro anti-tumor functions of CAR-T cells,leading to CAR-T cell therapy failure and disease progression in *** tumor microenvironments persisted before CAR-T cell therapy,during both cell expansion and disease progression,which could not be altered by infiltrating CAR-T *** metabolism profile of M2-subtype macrophages and those of dysfunctional T cells also contributed to the immunosuppressive tumor ***,our findings provided a clinical rationale for targeting tumor microenvironments and reprogramming immune cell metabolism as effective therapeutic strategies to prevent lymphoma relapse in future designs of CAR-T cell therapy.

关键词： anti-CD19 chimeric antigen receptor T immunotherapy diffuse large B cell lymphoma tumor microenvironment tumor-associated macrophage metabolism