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| 1 | Single-cell atlas reveals a distinct immune profile fostered by T cell-B cell crosstalk in triple negative breast cancer显示文摘Background:Characterizing the unique immune microenvironment of each tumor is of great importance for better predicting prognosis and guiding cancer immunotherapy.However,the unique features of the immune microenvironment of triple negative breast cancer(TNBC)compared with other subtypes of breast cancer remain elusive.Therefore,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 cancer.Methods:Single-cell RNA sequencing(scRNA-seq)was performed on CD45^(+)immune cells isolated from human normal breast tissues and primary breast tumors of various subtypes.By 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 cancer.Pseudotime and cell-cell communication analyses were also conducted to characterize the immune microenvironment.Results: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 cells.Tregs and exhausted CD8+T cells in TNBC exhibited increased immunosuppression signature and dysfunctional scores.Pseudotime analyses showed that B cells tended to differentiate to plasma cells in TNBC.Cell-cell communication analyses indicated that these unique features are fostered by the diversified T cell-B cell crosstalk in TNBC.Based on the T cell-B cell crosstalk,a prognostic signaturewas established that could effectively predict the prognosis status for patients with TNBC.Additionally,it was found that TNBC had a higher proportion of cytotoxic natural killer(NK)cells,whereas HER2^(+)or luminal-like breast cancer lost this feature,suggesting thatHER2^(+)or luminal-like breast cancer,but not TNBC,may benefit from NK-based immunotherapy.Conclusions:This study identified a distinct immune feature fostered by T cell-B cell crosstalk in TNBC,which provides better prognostic information and effective therapeutic targets for breast cancer. | Shuning Ding Niu Qiao Qingchen Zhu Yiwei Tong Shengyue Wang Xiaosong Chen Qiang Tian Yichuan Xiao Kunwei Shen | 2023 | Cancer Communications2023，43，6： | 2 |
| 2 | Biomarkers of aging显示文摘Aging biomarkers are a combination of biological parameters to(i)assess age-related changes,(ii)track the physiological aging process,and(iii)predict the transition into a pathological status.Although a broad spectrum of aging biomarkers has been developed,their potential uses and limitations remain poorly characterized.An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research:How old are we?Why do we get old?And how can we age slower?This review aims to address this need.Here,we summarize our current knowledge of biomarkers developed for cellular,organ,and organismal levels of aging,comprising six pillars:physiological characteristics,medical imaging,histological features,cellular alterations,molecular changes,and secretory factors.To fulfill all these requisites,we propose that aging biomarkers should qualify for being specific,systemic,and clinically relevant. | Aging Biomarker Consortium Hainan Bao Jiani Cao Mengting Chen Min Chen Wei Chen Xiao Chen Yanhao Chen Yu Chen Yutian Chen Zhiyang Chen Jagadish K Chhetri Yingjie Ding Junlin Feng Jun Guo Mengmeng Guo Chuting He Yujuan Jia Haiping Jiang Ying Jing Dingfeng Li Jiaming Li Jingyi Li Qinhao Liang Rui Liang Feng Liu Xiaoqian Liu Zuojun Liu Oscar Junhong Luo Jianwei Lv Jingyi Ma Kehang Mao Jiawei Nie Xinhua Qiao Xinpei Sun Xiaoqiang Tang Jianfang Wang Qiaoran Wang Siyuan Wang Xuan Wang Yaning Wang Yuhan Wang Rimo Wu Kai Xia Fu-Hui Xiao Lingyan Xu Yingying Xu Haoteng Yan Liang Yang Ruici Yang Yuanxin Yang Yilin Ying Le Zhang Weiwei Zhang Wenwan Zhang Xing Zhang Zhuo Zhang Min Zhou Rui Zhou Qingchen Zhu Zhengmao Zhu Feng Cao Zhongwei Cao Piu Chan Chang Chen Guobing Chen Hou-Zao Chen Jun Chen Weimin Ci Bi-Sen Ding Qiurong Ding Feng Gao Jing-Dong JHan Kai Huang Zhenyu Ju Qing-Peng Kong Ji Li Jian Li Xin Li Baohua Liu Feng Liu Lin Liu Qiang Liu Qiang Liu Xingguo Liu Yong Liu Xianghang Luo Shuai Ma Xinran Ma Zhiyong Mao Jing Nie Yaojin Peng Jing Qu Jie Ren Ruibao Ren Moshi Song Zhou Songyang Yi Eve Sun Yu Sun Mei Tian Shusen Wang Si Wang Xia Wang Xiaoning Wang Yan-Jiang Wang Yunfang Wang Catherine CL Wong Andy Peng Xiang Yichuan Xiao Zhengwei Xie Daichao Xu Jing Ye Rui Yue Cuntai Zhang Hongbo Zhang Liang Zhang Weiqi Zhang Yong Zhang Yun-Wu Zhang Zhuohua Zhang Tongbiao Zhao Yuzheng Zhao Dahai Zhu Weiguo Zou Gang Pei Guang-Hui Liu | 2023 | Science China(Life Sciences)2023，66，5： | 2 |
| 3 | Identification of cross-reactive CD8^(+)T cell receptors with high functional avidity to a SARS-CoV-2 immunodominant epitope and its natural mutant variants显示文摘Despite the growing knowledge of T cell responses in COVID-19 patients,there is a lack of detailed characterizations for T cell-antigen interactions and T cell functions.Here,with a predicted peptide library from SARS-CoV-2 S and N proteins,we found that specific CD8+T cell responses were identified in over 75%of COVID-19 convalescent patients(15/20)and an epitope from the N protein,N361-369(KTFPPTEPK),was the most dominant epitope from our selected peptide library.Importantly,we discovered 2 N361-369-specific T cell receptors(TCRs)with high functional avidity that were independent of the CD8 co-receptor.These TCRs exhibited complementary cross-reactivity to several presently reported N361-369 mutant variants,as to the wild-type epitope.Further,the natural functions of these TCRs in the cytotoxic immunity against SARS-CoV-2 were determined with dendritic cells(DCs)and the lung organoid model.We found that the N361-369 epitope could be normally processed and endogenously presented by these different types of antigen presenting cells,to elicit successful activation and effective cytotoxicity of CD8+T cells ex vivo.Our study evidenced potential mechanisms of cellular immunity to SARS-CoV-2,and illuminated potential ways of viral clearance in COVID-19 patients.These results indicate that utilizing CD8-independent TCRs against SARS-CoV-2-associated antigens may provide functional superiority that is beneficial for the adoptive cell immunotherapies based on natural or genetically engineered T cells.Additionally,this information is highly relevant for the development of the next-generation vaccines with protections against continuously emerged SARS-CoV-2 mutant strains. | Chao Hu Meiying Shen Xiaojian Han Qian Chen Luo Li Siyin Chen Jing Zhang Fengxia Gao Wang Wang Yingming Wang Tingting Li Shenglong Li Jingjing Huang Jianwei Wang Ju Zhu Dan Chen Qingchen Wu Kun Tao Da Pang Aishun Jin | 2022 | Genes & Diseases2022，9，1： | 0 |
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