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| 1 | Defined tumor antigen-specific T cells potentiate personalized TCR-T cell therapy and prediction of immunotherapy response显示文摘Personalized immunotherapy targeting tumor-specific antigens(TSAs)could generate efficient and safe antitumor immune response without damaging normal tissues.Although neoantigen vaccines have shown therapeutic effect in clinic trials,precise prediction of neoantigens from tumor mutations is still challenging.The host antitumor immune response selects and activates T cells recognizing tumor antigens.Hence,T cells engineered with T-cell receptors(TCRs)from these naturally occurring tumor antigen-specific T(Tas)cells in a patient will target personal TSAs in his/her tumor.To establish such a personalized TCR-T cell therapy,we comprehensively characterized T cells in tumor and its adjacent tissues by single-cell mRNA sequencing(scRNA-seq),TCR sequencing(TCR-seq)and in vitro neoantigen stimulation.Compared to bystander T cells circulating among tissues,Tas cells were characterized by tumor enrichment,tumor-specific clonal expansion and neoantigen specificity.We found that CXCL13 is a unique marker for both CD4^(+)and CD8^(+)Tas cells.Importantly,TCR-T cells expressing TCRs from Tas cells showed significant therapeutic effects on autologous patient-derived xenograft(PDX)tumors.Intratumoral Tas cell levels measured by CXCL13 expression precisely predicted the response to immune checkpoint blockade,indicating a critical role of Tas cells in the antitumor immunity.We further identified CD200 and ENTPD1 as surface markers for CD4^(^(+))and CD8^(^(+))Tas cells respectively,which enabled the isolation of Tas cells from tumor by Fluorescence Activating Cell Sorter(FACS)sorting.Overall,our results suggest that TCR-T cells engineered with Tas TCRs are a promising agent for personalized immunotherapy,and intratumoral Tas cell levels determine the response to immunotherapy. | Jingjing He Xinxin Xiong Han Yang Dandan Li Xuefei Liu Shuo Li Shuangye Liao Siyu Chen Xizhi Wen Kuai Yu Lingyi Fu Xingjun Dong Kaiyu Zhu Xiaojun Xia Tiebang Kang Chaochao Bian Xiang Li Haiping Liu Peirong Ding Xiaoshi Zhang Zhenjiang Liu Wende Li Zhixiang Zuo Penghui Zhou | 2022 | Cell Research2022，32，6： | 10 |
| 2 | Allotransplantation of adult spinal cord tissues after complete transected spinal cord injury: long-term survival and functional recovery in canines显示文摘Spinal cord injury(SCI), especially complete transected SCI, leads to loss of cells and extracellular matrix and functional impairments. In a previous study, we transplanted adult spinal cord tissues(aSCTs) to replace lost tissues and facilitate recovery in a rat SCI model. However, rodents display considerable differences from human patients in the scale, anatomy and functions of spinal cord systems, and responses after injury. Thus, use of a large animal SCI model is required to examine the repair efficiency of potential therapeutic approaches. In this study, we transplanted allogenic aSCTs from adult dogs to the lesion area of canines after complete transection of the thoracic spinal cord, and investigated the long-term cell survival and functional recovery. To enhance repair efficiency, a growth factor cocktail was added during aSCT transplantation, providing a favorable microenvironment. The results showed that transplantation of a SCTs, in particular with the addition of growth factors, significantly improves locomotor function restoration and increases the number of neurofilament-, microtubule-associated protein2-, 5-hydroxytryptamine-, choline acetyltransferase-and tyrosine hydroxylase-positive neurons in the lesion area at 6 months post-surgery. In addition, we demonstrated that donor neurons in a SCTs can survive for a long period after transplantation. This study showed for the first time that transplanting aSCTs combined with growth factor supplementation facilitates reconstruction of injured spinal cords, and consequently promotes long lasting motor function recovery in a large animal complete transected SCI model, and therefore could be considered as a possible therapeutic strategy in humans. | He Shen Shuyu Wu Xi Chen Bai Xu Dezun Ma Yannan Zhao Yan Zhuang Bing Chen Xianglin Hou Jiayin Li Yudong Cao Xianyong Fu Jun Tan Wen Yin Juan Li Li Meng Ya Shi Zhifeng Xiao Xingjun Jiang Jianwu Dai | 2020 | Science China(Life Sciences)2020，63，12： | 3 |
| 3 | Cloning and Bioinformatics Analysis of hcp Gene in Aeromonas hydrophila显示文摘[Objectives]To explore the function of hcp gene in Aeromonas hydrophila.[Methods]A pair of specific primers was designed referring to the hcp gene sequence of A.hydrophila.The hcp gene was amplified by PCR,and performed bioinformatics analysis.[Results]The hcp gene had a total length of 1650 bp and encoded 549 amino acids.The theoretical molecular weight of the protein predicted was about 59476.44 kDa.After predicting the N-terminal signal peptide structure of the amino acid sequence,neither obvious signal peptide cleavage site nor signal peptide was found,and the protein had no transmembrane region.The amino acid sequence had a N-glycosylation site,4 protein kinase C phosphorylation sites,7 casein kinase II phosphorylation sites,9 N-myristoylation sites,4 isoprene binding sites,10 microbody C-terminal target signal sites,and an ATP/GTP binding site motif A(P-ring).The amino acid sequence of hcp gene of A.hydrophila was performed homology analysis with other Aeromonas strains,and it showed higher homology with A.veronii.In the secondary structure,theα-helix,β-sheet,random coil and extended strand accounted for 45.36%,6.01%,37.52%and 11.11%,respectively.The tertiary structure model consisted of 18α-helix and 22β-sheet.Analysis of protein-protein network interaction demonstrated that the proteins interacting with Hcp protein were AHA_3407,nrfA,nirB-1,nirB-2 and AHA_1112.[Conclusions]Through the bioinformatics prediction results,the basic information of hcp gene of A.hydrophila is preliminarily understood,and the possible function of this protein is predicted,in order to provide guidance for subsequent vaccine research. | Fan LI Xingjun FU Haiyun FENG Shi WANG Weijie ZHANG Huanying PANG Na WANG | 2024 | Asian Agricultural Research2024，16，3： | 0 |
| 4 | Proton radiation effects on high-speed silicon Mach-Zehnder modulators for space application显示文摘In this paper,performance degradation effects on high-speed silicon Mach-Zehnder modulators under proton radiation were investigated for future space environment applications.The test devices were exposed to 3-MeV protons of three fluence levels(5×10,2×10,and 5×10ions/cm~2),which is comparable to the radiation amount for operating in a harsh space environment after several decades.The performance of the silicon modulator after radiation was characterized in terms of modulation efficiency and eye diagram.The results illustrate that the modulation efficiency is significantly reduced after proton radiation and shows an obvious decrease with increasing radiation fluence.The extinction ratios of the on-off keying(OOK)eye diagram are obviously dropped with increasing radiation fluence and correspond well to modulation efficiency degradation.Furthermore,three representative states for data transmission are demonstrated under three fluences,from still working to the critical state and eventually complete fail.Displacement damage and ionization damage are the two major mechanisms during proton radiation,which lead to the bulk defects and accumulating defect charges and cause performance degradation of silicon Mach-Zehnder modulators. | Changhao HAN Zhaoyi HU Yuansheng TAO Engang FU Yandong HE Fenghe YANG Jun QIN Xingjun WANG | 2022 | Science China(Information Sciences)2022，65，12： | 0 |
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