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Features and therapeutic potential of t-cell receptors in high-grade glioma

Chinese Medical Journal 2019年第12期132卷 1435-1440页

作者： Jie-Lin Zhang Xiao-Song Zhong Shou-Bo Yang Xun Kang Yan Li Jian-Xin Chen Wen-Bin Li General Department of Neuro-oncology Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China the Clinical Center of Gene and cell Engineering Beijing Shijitan HospitalCapital Medical UniversityBeijing 100038China Department of Glioma Beijing Shijitan HospitalCapital Medical UniversityBeijing 100038China

Background: Previous studies have shown that endogenous t cells play an important role in the prolonged survival time of highgrade glioma (HGG) patients. Our objectives were to investigate the features of t-cell receptor (tCR) repertoires in HGG patients and to elucidate any potential therapeutic value. Methods: During November 2011 and December 2018, tumor tissues and blood samples of 35 patients with HGG who underwent surgery at Beijing tiantan Hospital or Beijing Shijitan Hospital were selected after surgery. After isolating DNA from samples, multiple rounds of PCR were performed to establish a DNA immune repertoire (IR). then, the sequences and frequencies of the complementarity-determining 3 (CDR3) region in tCR beta chain (tRB) were identified by high-throughput sequencing and IR analysis. A survival follow-up was conducted monthly thereafter until December 2018. Finally, the t test and Mann-Whitney test were used to compare statistical differences between two sets of data. Results: the Shannon diversity index (SHDI) of tRB sequences of HGG patients was significantly lower than that of healthy individuals (7.34 vs. 8.45, P = 0.001). the SHDI of tRB sequences of glioblastoma (GBM) patients with more than 16 months survival time was much higher than that of GBM patients with shorter survival times in both tumor tissues (3.48 ± 0.31 vs. 6.21 ± 0.33, t =-5.49, P = 0.002) and blood cells (6.02 ± 0.66 vs. 7.44 ± 0.32, t =-2.20, P = 0.036). In addition, patients achieved a distinctly higher proportion compared to that of healthy individuals in the proportion of tRBV9 and tRBV5 functional regions (9.83% vs. 6.83%, P = 0.001). Surgical tissue from patients who survived more than 16 months yielded a much higher proportion of tRBV4 and tRBV9 regions (7.14% vs. 3.28%, t = 3.18, P = 0.019). In surgical tissues from two GBM patients who survived for longer than 46 months, we found a potentially therapeutic tCR sequence. Conclusions: HGG patients have less species diversity

关键词： Glioma t-cell receptor Immunotherapy Survival therapeutics

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Advances in the development of chimeric antigen receptor-t-cell therapy in B-cell acute lymphoblastic leukemia

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Chinese Medical Journal 2020年第4期133卷 474-482页

作者： Xian Zhang Jing-Jing Li Pei-Hua Lu Department of Hematology Lu Daopei HospitalLangfangHebei 065201China Lu Daopei Institute of Hematology Beijing 100176China

CD19-targeted chimeric antigen receptor t-cell(CAR-t)therapy is effective in refractory/relapsed(R/R)B-cell acute lymphoblastic leukemia(B-ALL).this review focuses on achievements,current obstacles,and future directions in CAR-t research.A high complete remission rate of 68%to 93%could be achieved after anti-CD19 CAR-t treatment for *** release syndrome and CAR-t-related neurotoxicity could be *** view of difficulties collecting autologous lymphocytes,universal CAR-t is a direction to *** the high relapse rate after anti-CD19 CAR-t therapy,the main solutions have been developing new targets including CD22 CAR-t,or CD19/CD22 dual ***,some studies showed that bridging into transplant post-CAR-t could improve leukemia-free *** patients who did not respond to CAR-t therapy were found to have an abnormal conformation of the CD19 exon or ***-CD19 CAR-t therapy for R/R B-ALL is *** individual to universal CAR-t,from one target to multi-targets,CAR-t-cell has a chance to be off the shelf in the future.

关键词： Chimeric antigen receptor t-cell B-cell acute lymphoblastic leukemia Complete remission Cytokine release syndrome Relapse transplantation

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Prognostic significance of locally invaded sites and tissue types in patients with nasal extranodal natura-killer/t-cell lymphoma: a single-center retrospective analysis

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Chinese Medical Journal 2019年第11期132卷 1305-1313页

作者： Ge-Hong Dong Yong Li Ji-Yong Dong Xue Li Hong-Fei Wan Lei Yang Jing-Wen Wang Li-Ping Gong Yi-Hua Zhao Hong Zhang Zi-Fen Gao Hong-Gang Liu Departm ent of Pathology Beijing Tiantan Hospital Capital Medical University Beijing 100070 China Department of Pathology Beijing Tongren Hospital Capital Medical University Beijing 100730 China Beijing Key Laboratory of Head and Neck Molecular Diagnostic Pathology Capital Medical University Beijing 100730 China Department of Radiology Beijing Tongren Hospital Capital Medical University Beijing 100730 China Department of Hematology Beijing Tongren Hospital Capital Medical University Beijing 100730 China Department of Pathology School of Basic Medical of Capital Medical University Beijing 100069 China

Background:Extranodal natural killer/t-cell lymphoma (ENKtL), nasal type, is an aggressive entity within the World Health Organization classification of lymphoid tumors. the International Prognostic Index is reported to be prognostically meaningful for ENKtL, but lacks discriminatory power for stage Ⅰ/Ⅱ ENKtL with extensive local invasion. this study aimed to evaluate the prognostic effects of local invasion by site and tissue type in patients with ENKtL. Methods: We retrospectively analyzed data of 86 patients who were diagnosed with ENKtL by the Department of Pathology of Beijing tongren Hospital from June 2002 to April 2016, and ascertained tumor infiltration of adjacent structures (AS), bone, and soft tissue for each patient, using physical findings and imaging scans. We used univariate and multivariate analysis to assess the association of each involved tissue or site with patients5 overall survival (OS). Results: Of the 86 patients, 71(82.6%) experienced invasion of AS, 22(25.6%) of soft tissue, and 26(30.2%) had bone involvement. Overall, patients with AS involvement did not show significantly shorter survival than those without AS involvement (Log rank X^2 = 1.177, P = 0.278);however, patients who had involved eyeballs or brains showed significantly lower 2-year OS rates than those without eyeball involvement (Log rank x^2 = 4.105, P = 0.043) or brain involvement (Log rank x^2 = 7.126, P = 0.008). Patients with involved local soft tissue or bones, respectively, showed lower 2-year OS rates than those without involved local soft tissue (Log rank x^2 = 10.390, P = 0.001) or bones (Log rank x^2 = 8.993, P = 0.003). Multivariate analysis showed that involvement of the cheek or facial muscles (hazard ratio, HR = 5.471, 95% confidence interval [Cl]: 1.466-20.416, P = 0.011) and the maxilla bone (HR = 6.120, 95% Cl: 1.517-24.694, P = 0.011) were significantly independent predictors of lower 2-year OS rates. Conclusions: Imaging can accurately detect ENKtL invasion

关键词： Lymphoma Natural killer cells t-cell Neoplasm Invasiveness Prognosis

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t-cell Co-inhibitory Molecules in Sepsis-induced Immunosuppression： From Bench to Bedside

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Chinese Medical Journal 2017年第10期130卷 1249-1252页

作者： Jian-Feng Xie Hai-Bo Qiu Yi Yang Department of Critical Care Medicine Nanjing Zhongda Hospital School of Medicine Southeast University Nanjing Jiangsu 210009 China

Sepsis, which is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, is a leading cause of death in the Intensive Care Unit （ICU） Epidemiological studies have shown tha... 详细信息

关键词： Co-inhibitory Molecules Immunosuppression Sepsis t-cell

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Relationship between t-cell receptor α gene polymorphisms and symptomatic differences in patients with narcolepsy type 1

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Chinese Medical Journal 2019年第15期132卷 1796-1801页

作者： Hui Ouyang Fang Han Ze-Chen Zhou Qi-Wen Zheng Yang-Yang Wang Jun Zhang Department of Clinical Neurology Peking University People's Hospital Beijing 100044 China Department of Clinical Pulmonology Peking University People's Hospital Beijing 100044 China Department of Epidemiology and Biostatistics School of Public Health Peking University Health Science Center Beijing 100191 China

Background:Recent genome-wide association studies have identified an important role of t-cell receptor α(tRA) gene in the development of narcolepsy type ***,the role of tRA haplotype polymorphisms in the symptomatic diversity of narcolepsy remains *** study aimed to investigate whether tRA polymorphisms can influence the symptomatic diversity of ***:totally,903 patients with narcolepsy type 1 were included in the *** were divided into different groups according to their ***,13 genotyped single nucleotide polymorphisms in the tRA were assessed for their association with symptoms of *** used the Chi-square test to determine differences in genotype frequencies in patients with ***,we identified the haplotypes and variations of the tRA and tested their association with the symptoms of narcolepsy using a logistic regression ***:According to the results of the logistic regression,tRA haplotypes tG and Ct were significantly associated with auditory hallucination,with odds ratios of 1.235 (95% confidence interval [CI],1.012-1.507) and 1.236 (95% CI,1.012-1.511),respectively (P tusions:the patterns of haplotype in tRA (haplotypes tG and Ct) are associated with hypnagogic auditory hallucination in patients with narcolepsy type ***,further studies are needed to confirm our results and explore the underlying mechanisms.

关键词： Narcolepsy t-cell receptor α gene Symptomatic subtype Haplotype Precision medicine

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Finding an Effective Distance Between t-cell and B-cell Using S/W ARQ in an Immune System Communication

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China Communications 2020年第1期17卷 174-185页

作者： Sanjit Ningthoujam tekcham Chingkheinganba Swarnendu K Chakraborty Dept.of Computer Science and Engineering NIT Arunachal Pradesh

In this paper,we present the effective distance between t-cell and B-cell in an immune system using Stop and Wait(S/W)Automatic Repeat Request(ARQ).the concentration of the molecules can be increased by increasing the transmitting number of molecules but it may reduce the performance of communication due to higher collision or interference with other *** is also reported in the literature that the concentration of the emitted molecules reduces if the distance from transmitter(tx)to Receiver(Rx)***,this paper mainly focuses on enhancing the receiver’s capture probability and higher successful complete transmission of the desired molecules by obtaining the effective distance from t-cell to *** order to find the effective distance,t-cell transmits the molecules 1(Interleukins-2)to B-cell,upon successful reception of molecules 1,antibodies(molecules 2)transmit back to ***,the effective distance of an immune system can be obtained after t-cell detects the concentration of the molecules 2 with respect to *** schemes of S/W ARQ protocols have implemented in Molecular Communication(MC)but it requires retransmission of duplicate copies due to the lack of addressing an effective ***,the simulations are performed in MAtLAB and the results obtain higher capture probability and also successful complete transmission of the desired molecules.

关键词： t-cell B-cell MC antigens antibodies diffusion coefficient(D) round trip time(Rtt)

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Human t-cell immunity against the emerging and re-emerging viruses

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Science China(Life Sciences) 2017年第12期60卷 1307-1316页

作者： Min Zhao Hangjie Zhang Kefang Liu George F.Gao William J.Liu Research Network of lmmunity and Health(RN1H) Beijing Institutes of Life ScienceChinese Academy of SciencesBeijing 100101China Key Laboratory of Medical Virology and Viral Diseases Ministry of Health of People's Republic of ChinaNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China

Over the past decade, we have seen an alarming number of high-profile outbreaks of newly emerging and re-emerging *** outbreaks of avian influenza viruses, Middle East respiratory syndrome coronaviruses, Zika virus and Ebola virus present great threats to global health. Considering the pivotal role of host t-cell immunity in the alleviation of symptoms and the clearance of viruses in patients, there are three issues to be primarily concerned about t-cell immunity when a new virus emerges: first, does the population possess pre-existing t-cells against the new virus through previous infections of genetically relevant viruses; second, does a proper immune response arise in the patients to provide protection through an immunopathogenic effect; lastly, how long can the virus-specific immune memory persist. Herein, we summarize the current updates on the characteristics of human t-cell immunological responses against recently emerged or re-emerged viruses, and emphasize the necessity for timely investigation on the t-cell features of these viral diseases, which may provide beneficial recommendations for clinical diagnosis and vaccine development.

关键词： emerging viruses avian influenza H7N9 MERS-CoV Zika Ebola human immunity t-cell cross-reactivity

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Multiprimer──PCR　for　screening　of　IgH　and　t-cell　receptor　rearranged　genes　in　　acute　lymphoblastic　l

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Chinese Medical Journal 1997年第2期110卷 100-103页

作者：徐兵周淑芸孙竞 DepartmentofHematoloy NanfangHospitaltheFirstMilitaryMedicalUniversity

Ｍｕｌｔｉｐｒｉｍｅｒ──ＰＣＲｆｏｒｓｃｒｅｅｎｉｎｇｏｆＩｇＨａｎｄＴ－ｃｅｌｌｒｅｃｅｐｔｏｒｒｅａｒｒａｎｇｅｄｇｅｎｅｓｉｎａｃｕｔｅｌｙｍｐｈｏｂｌａｓｔｉｃｌｅｕｋｅｍｉａＸｕＢｉｎｇ徐兵，ＺｈｏｕＳｈ... 详细信息

Ｍｕｌｔｉｐｒｉｍｅｒ──ＰＣＲｆｏｒｓｃｒｅｅｎｉｎｇｏｆＩｇＨａｎｄＴ－ｃｅｌｌｒｅｃｅｐｔｏｒｒｅａｒｒａｎｇｅｄｇｅｎｅｓｉｎａｃｕｔｅｌｙｍｐｈｏｂｌａｓｔｉｃｌｅｕｋｅｍｉａＸｕＢｉｎｇ徐兵，ＺｈｏｕＳｈｕｙｕｎ周淑芸ａｎｄｓｕｎＪｉｎｇ...

关键词： lymphoblastic screening PCR t-cell acute and for genes in IgH

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Extranodal natural killer/t-cell lymphoma(nasal type) presenting as a perianal abscess: A case report

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World Journal of Clinical Cases 2019年第8期7卷 992-1000页

作者： Yan-Ni Liu Yong Zhu Jia-Jun tan Guang-Shu Shen Shu-Liang Huang Chun-Gen Zhou Shao-Hua Huangfu Rui Zhang Xiao-Bo Huang Ling Wang Qi Zhang Bin Jiang Nanjing University of Chinese Medicine Department of Colorectal Surgery The Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine Department of Pathology The Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine Department of Medical Imaging The Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine

BACKGROUND Extranodal natural killer(NK) t-cell lymphoma(ENKtL), nasal type is a rare subtype of extranodal non-Hodgkin lymphoma characterized by vascular damage and necrosis. the lesions usually present in the nasal cavity and adjacent tissues, however, the disease originates from the gastrointestinal or genitourinary tract in 25% of cases. Since rectal involvement in ENKtL is rare, rectal symptoms in the course of ENKtL are often misdiagnosed and considered to be related to benign diseases such as rectal fistula or perianal *** SUMMARY We report the case of a 24-year-old Han Chinese female who initially presented with a perianal abscess that was subsequently diagnosed as nasal type *** to typical perianal pain, perianal abscess was diagnosed and surgical incision and drainage were performed. After recurrent, severe anal hemorrhages leading to hypovolemic shock and multiple surgeries, a diagnosis of ENKtL was made. the patient's condition gradually deteriorated, and she died shortly after initiation of *** Systemic and neoplastic diseases should be included in the differential diagnosis of any potentially benign perianal abscess complicated with recurrent hemorrhages.

关键词： Extranodal natural killer t-cell lymphoma Perianal abscess Lymphoma Rectal involvement Case report

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Prediction of promiscuous t-cell epitopes in the Zika virus polyprotein:An in silico approach

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Asian Pacific Journal of tropical Medicine 2016年第9期9卷 822-828页

作者： Hamza Dar tahreem Zaheer Muhammad talha Rehman Amjad Ali Aneela Javed Gohar Ayub Khan Mustafeez Mujtaba Babar Yasir Waheed Atta-ur-Rahman School of Applied Biosciences(ASAB) National University of Sciences and Technology Shifa College of Pharmaceutical Sciences Shifa Tameer-e-Millat University Foundation University Medical College Foundation University Islamabad

Objective:to predict immunogenic promiscuous t-cell epitopes from the polyprotein of the Zika virus using a range of bioinformatics *** date,no epitope data are available for the Zika virus in the IEDB ***:We retrieved nearly 54 full length polyprotein sequences of the Zika virus from the NCBI database belonging to different outbreaks.A consensus sequence was then used to predict the promiscuous t cell epitopes that bind MHC 1 and MHC II alleles using Propred1 and Propred immunoinformatic algorithms *** antigencity predicted score was also calculated for each predicted epitope using the Vaxi Jen 2.0 ***:By using Pro Pred1,23 antigenic epitopes for HLA class I and 48 antigenic epitopes for HLA class II were predicted from the consensus polyprotein sequence of Zika *** greatest number of MHC class I binding epitopes were projected within the NS5(21%),followed by Envelope(17%).For MHC class II,greatest number of predicted epitopes were in NS5(19%) followed by the Envelope,NS1 and NS2(17% each).A variety of epitopes with good binding affinity,promiscuity and antigenicity were predicted for both the HLA ***:the predicted conserved promiscuous t-cell epitopes examined in this study were reported for the first time and will contribute to the imminent design of Zika virus vaccine candidates,which will be able to induce a broad range of immune responses in a heterogeneous HLA ***,our results can be verified and employed in future efficacious vaccine formulations only after successful experimental studies.

关键词： Zika Virus B-cell Epitopes t-cell Epitopes Vaccine Antigenicity

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