应激反应调节因子 HSF1 可调节自然杀伤细胞的抗肿瘤免疫力

IF 17.3 1区 生物学 Q1 CELL BIOLOGY Nature Cell Biology Pub Date : 2024-09-02 DOI:10.1038/s41556-024-01490-z
Kathryn Hockemeyer, Theodore Sakellaropoulos, Xufeng Chen, Olha Ivashkiv, Maria Sirenko, Hua Zhou, Giovanni Gambi, Elena Battistello, Kleopatra Avrampou, Zhengxi Sun, Maria Guillamot, Luis Chiriboga, George Jour, Igor Dolgalev, Kate Corrigan, Kamala Bhatt, Iman Osman, Aristotelis Tsirigos, Nikos Kourtis, Iannis Aifantis
{"title":"应激反应调节因子 HSF1 可调节自然杀伤细胞的抗肿瘤免疫力","authors":"Kathryn Hockemeyer, Theodore Sakellaropoulos, Xufeng Chen, Olha Ivashkiv, Maria Sirenko, Hua Zhou, Giovanni Gambi, Elena Battistello, Kleopatra Avrampou, Zhengxi Sun, Maria Guillamot, Luis Chiriboga, George Jour, Igor Dolgalev, Kate Corrigan, Kamala Bhatt, Iman Osman, Aristotelis Tsirigos, Nikos Kourtis, Iannis Aifantis","doi":"10.1038/s41556-024-01490-z","DOIUrl":null,"url":null,"abstract":"Diverse cellular insults converge on activation of the heat shock factor 1 (HSF1), which regulates the proteotoxic stress response to maintain protein homoeostasis. HSF1 regulates numerous gene programmes beyond the proteotoxic stress response in a cell-type- and context-specific manner to promote malignancy. However, the role(s) of HSF1 in immune populations of the tumour microenvironment remain elusive. Here, we leverage an in vivo model of HSF1 activation and single-cell transcriptomic tumour profiling to show that augmented HSF1 activity in natural killer (NK) cells impairs cytotoxicity, cytokine production and subsequent anti-tumour immunity. Mechanistically, HSF1 directly binds and regulates the expression of key mediators of NK cell effector function. This work demonstrates that HSF1 regulates the immune response under the stress conditions of the tumour microenvironment. These findings have important implications for enhancing the efficacy of adoptive NK cell therapies and for designing combinatorial strategies including modulators of NK cell-mediated tumour killing. Hockemeyer et al. demonstrate that HSF1 activation inhibits cytokine production and cytotoxic activity in NK cells to impair anti-tumour immune responses.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 10","pages":"1734-1744"},"PeriodicalIF":17.3000,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The stress response regulator HSF1 modulates natural killer cell anti-tumour immunity\",\"authors\":\"Kathryn Hockemeyer, Theodore Sakellaropoulos, Xufeng Chen, Olha Ivashkiv, Maria Sirenko, Hua Zhou, Giovanni Gambi, Elena Battistello, Kleopatra Avrampou, Zhengxi Sun, Maria Guillamot, Luis Chiriboga, George Jour, Igor Dolgalev, Kate Corrigan, Kamala Bhatt, Iman Osman, Aristotelis Tsirigos, Nikos Kourtis, Iannis Aifantis\",\"doi\":\"10.1038/s41556-024-01490-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Diverse cellular insults converge on activation of the heat shock factor 1 (HSF1), which regulates the proteotoxic stress response to maintain protein homoeostasis. HSF1 regulates numerous gene programmes beyond the proteotoxic stress response in a cell-type- and context-specific manner to promote malignancy. However, the role(s) of HSF1 in immune populations of the tumour microenvironment remain elusive. Here, we leverage an in vivo model of HSF1 activation and single-cell transcriptomic tumour profiling to show that augmented HSF1 activity in natural killer (NK) cells impairs cytotoxicity, cytokine production and subsequent anti-tumour immunity. Mechanistically, HSF1 directly binds and regulates the expression of key mediators of NK cell effector function. This work demonstrates that HSF1 regulates the immune response under the stress conditions of the tumour microenvironment. These findings have important implications for enhancing the efficacy of adoptive NK cell therapies and for designing combinatorial strategies including modulators of NK cell-mediated tumour killing. Hockemeyer et al. demonstrate that HSF1 activation inhibits cytokine production and cytotoxic activity in NK cells to impair anti-tumour immune responses.\",\"PeriodicalId\":18977,\"journal\":{\"name\":\"Nature Cell Biology\",\"volume\":\"26 10\",\"pages\":\"1734-1744\"},\"PeriodicalIF\":17.3000,\"publicationDate\":\"2024-09-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nature Cell Biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.nature.com/articles/s41556-024-01490-z\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Cell Biology","FirstCategoryId":"99","ListUrlMain":"https://www.nature.com/articles/s41556-024-01490-z","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

热休克因子 1(HSF1)可调控蛋白毒性应激反应,以维持蛋白质平衡。除蛋白毒性应激反应外,HSF1 还以细胞类型和特定环境的方式调控许多基因程序,从而促进恶性肿瘤的发生。然而,HSF1 在肿瘤微环境免疫群体中的作用仍然难以捉摸。在这里,我们利用 HSF1 激活的体内模型和单细胞肿瘤转录组图谱分析表明,自然杀伤(NK)细胞中 HSF1 活性的增强会损害细胞毒性、细胞因子的产生和随后的抗肿瘤免疫。从机理上讲,HSF1 直接结合并调节 NK 细胞效应功能关键介质的表达。这项研究表明,HSF1 在肿瘤微环境的应激条件下调节免疫反应。这些发现对提高采用性 NK 细胞疗法的疗效以及设计包括 NK 细胞介导的肿瘤杀伤调节剂在内的组合策略具有重要意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
The stress response regulator HSF1 modulates natural killer cell anti-tumour immunity
Diverse cellular insults converge on activation of the heat shock factor 1 (HSF1), which regulates the proteotoxic stress response to maintain protein homoeostasis. HSF1 regulates numerous gene programmes beyond the proteotoxic stress response in a cell-type- and context-specific manner to promote malignancy. However, the role(s) of HSF1 in immune populations of the tumour microenvironment remain elusive. Here, we leverage an in vivo model of HSF1 activation and single-cell transcriptomic tumour profiling to show that augmented HSF1 activity in natural killer (NK) cells impairs cytotoxicity, cytokine production and subsequent anti-tumour immunity. Mechanistically, HSF1 directly binds and regulates the expression of key mediators of NK cell effector function. This work demonstrates that HSF1 regulates the immune response under the stress conditions of the tumour microenvironment. These findings have important implications for enhancing the efficacy of adoptive NK cell therapies and for designing combinatorial strategies including modulators of NK cell-mediated tumour killing. Hockemeyer et al. demonstrate that HSF1 activation inhibits cytokine production and cytotoxic activity in NK cells to impair anti-tumour immune responses.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Nature Cell Biology
Nature Cell Biology 生物-细胞生物学
CiteScore
28.40
自引率
0.90%
发文量
219
审稿时长
3 months
期刊介绍: Nature Cell Biology, a prestigious journal, upholds a commitment to publishing papers of the highest quality across all areas of cell biology, with a particular focus on elucidating mechanisms underlying fundamental cell biological processes. The journal's broad scope encompasses various areas of interest, including but not limited to: -Autophagy -Cancer biology -Cell adhesion and migration -Cell cycle and growth -Cell death -Chromatin and epigenetics -Cytoskeletal dynamics -Developmental biology -DNA replication and repair -Mechanisms of human disease -Mechanobiology -Membrane traffic and dynamics -Metabolism -Nuclear organization and dynamics -Organelle biology -Proteolysis and quality control -RNA biology -Signal transduction -Stem cell biology
期刊最新文献
FMRP gains mitochondrial fission control Chromatin remodelling in damaged intestinal crypts orchestrates redundant TGFβ and Hippo signalling to drive regeneration FMRP regulates MFF translation to locally direct mitochondrial fission in neurons A systemic effect for liver senescence Hepatocellular senescence induces multi-organ senescence and dysfunction via TGFβ
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1