检索结果-南通市图书馆

LIM-domain-only 4(LMO4)enhances CD8^(+)T-cell stemness and tumor rejection by boosting IL-21-STAT3 signaling

Signal Transduction and Targeted Therapy 2024年第9期9卷 4066-4078页

作者： Roland C.Schelker Jessica Fioravanti Fabio Mastrogiovanni Jeremy G.Baldwin Nisha Rana Peng Li Ping Chen Timea Vadász Rosanne Spolski Christoph Heuser-Loy Dragana Slavkovic-Lukic Pedro Noronha Giuseppe Damiano Laura Raccosta Daniela Maggioni Sree Pullugula Jian-Xin Lin Jangsuk Oh Patrick Grandinetti Mario Lecce Leo Hesse Emilia Kocks Azucena Martín-Santos Claudia Gebhard William G.Telford Yun Ji Nicholas P.Restifo Vincenzo Russo Michael Rehli Wolfgang Herr Warren J.Leonard luca gattinoni Division of Functional Immune Cell Modulation Leibniz Institute for ImmunotherapyRegensburgGermany Center for Cancer Research National Cancer InstituteNational Institutes of HealthBethesdaMDUSA Laboratory of Molecular Immunology and the Immunology Center National HeartLung and Blood InstituteNational Institutes of HealthBethesdaMDUSA Department of Internal MedicineⅢ University Hospital RegensburgRegensburgGermany Next Generation Sequencing Core Leibniz Institute for ImmunotherapyRegensburgGermany Immuno-Biotherapy of Melanoma and Solid Tumors Unit Division of Experimental OncologyIRCCS Scientific Institute San RaffaeleMilanItaly Vita-Salute San Raffaele University MilanItaly University of Regensburg RegensburgGermany National Center for Tumor Diseases WERA SiteWürzburg-Erlangen-Regensburg-AugsburgGermany Center for Immunomedicine in Transplantation and Oncology University Hospital RegensburgRegensburgGermany

High frequencies of stem-like memory T cells in infusion products correlate with superior patient outcomes across multiple T cell therapy ***,we analyzed a published CRISPR activation screening to identify transcriptional regulators that could be harnessed to augment stem-like behavior in CD8^(+)T *** IFN-γproduction as a proxy for CD8^(+)T cell terminal differentiation,LMO4 emerged among the top hits inhibiting the development of effectors ***,we found that Lmo4 was downregulated upon CD8^(+)T cell activation but maintained under culture conditions facilitating the formation of stem-like T *** employing a synthetic biology approach to ectopically express LMO4 in antitumor CD8^(+)T cells,we enabled selective expansion and enhanced persistence of transduced cells,while limiting their terminal differentiation and ***4 overexpression promoted transcriptional programs regulating stemness,increasing the numbers of stem-like CD8^(+)memory T cells and enhancing their polyfunctionality and recall *** tested in syngeneic and xenograft tumor models,LMO4 overexpression boosted CD8^(+)T cell antitumor immunity,resulting in enhanced tumor *** than directly modulating gene transcription,LMO4 bound to JAK1 and potentiated STAT3 signaling in response to IL-21,inducing the expression of target genes(Tcf7,Socs3,Junb,and Zfp36)crucial for memory ***/Cas9-deletion of Stat3 nullified the enhanced memory signature conferred by LMO4,thereby abrogating the therapeutic benefit of LMO4 *** results establish LMO4 overexpression as an effective strategy to boost CD8^(+)T cell stemness,providing a new synthetic biology tool to bolster the efficacy of T cell-based immunotherapies.

关键词： STAT3 immunity LMO4

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：