• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

BxPC-3来源的小细胞外囊泡通过ATM-AMPK-沉默调节蛋白介导的FOXO核转位诱导FOXP3+调节性T细胞

BxPC-3-Derived Small Extracellular Vesicles Induce FOXP3+ Treg through ATM-AMPK-Sirtuins-Mediated FOXOs Nuclear Translocations.

作者信息

Shen Tao, Jia Shengnan, Ding Guoping, Ping Dongnan, Zhou Liangjing, Zhou Senhao, Cao Liping

机构信息

Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Innovation Center for Minimally Invasive Technique and Device, Zhejiang University, Hangzhou, China.

出版信息

iScience. 2020 Aug 21;23(8):101431. doi: 10.1016/j.isci.2020.101431. Epub 2020 Aug 2.

DOI:10.1016/j.isci.2020.101431
PMID:32798974
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7452591/
Abstract

Immunotherapy in pancreatic ductal adenocarcinoma (PDAC) treatment faces serious challenges, due particularly to the poor immunogenicity. Cancer cell-derived small extracellular vesicles (sEVs) play important roles in damaging the immune system. However, the effects of pancreatic cancer-derived sEVs on T lymphocytes are unknown. Here we investigated changes in phenotypes and signal transduction pathways in sEVs-treated T lymphocytes. We identified the overexpression of immune checkpoint proteins PD-1, PD-L1, CTLA4, and Tim-3 and the enrichment of FOXP3+ Treg cluster in sEVs-treated T lymphocytes by CyTOF. Gene set enrichment analysis revealed that DNA damage response and metabolic pathways might be involved in sEVs-induced Tregs. ATM, AMPK, SIRT1, SIRT2, and SIRT6 were activated sequentially in sEVs-treated T lymphocytes and essential for sEVs-upregulated expressions of FOXO1A, FOXO3A, and FOXP3. Our study reveals the impact and mechanism of pancreatic cancer cell-derived sEVs on T lymphocytes and may provide insights into developing immunotherapy strategies for PDAC treatment.

摘要

胰腺导管腺癌（PDAC）治疗中的免疫疗法面临严峻挑战，尤其是由于免疫原性较差。癌细胞衍生的小细胞外囊泡（sEVs）在破坏免疫系统方面发挥着重要作用。然而，胰腺癌衍生的sEVs对T淋巴细胞的影响尚不清楚。在此，我们研究了sEVs处理的T淋巴细胞的表型和信号转导途径的变化。我们通过质谱流式细胞术（CyTOF）鉴定了sEVs处理的T淋巴细胞中免疫检查点蛋白PD-1、PD-L1、CTLA4和Tim-3的过表达以及FOXP3 + Treg簇的富集。基因集富集分析表明，DNA损伤反应和代谢途径可能参与了sEVs诱导的Tregs。在sEVs处理的T淋巴细胞中，ATM、AMPK、SIRT1、SIRT2和SIRT6依次被激活，并且对于sEVs上调FOXO1A、FOXO3A和FOXP3的表达至关重要。我们的研究揭示了胰腺癌细胞衍生的sEVs对T淋巴细胞的影响及其机制，并可能为开发PDAC治疗的免疫疗法策略提供见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb22/7452591/1e427df4dd1a/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb22/7452591/6fe94b9dbb6f/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb22/7452591/0beddafa42b1/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb22/7452591/6d9a1f9f9901/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb22/7452591/8f286f59e1f6/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb22/7452591/5be14b902d01/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb22/7452591/22fddc45ecce/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb22/7452591/f2e310ebd127/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb22/7452591/8888a1b2cefd/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb22/7452591/32ce76e0c8da/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb22/7452591/1e427df4dd1a/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb22/7452591/6fe94b9dbb6f/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb22/7452591/0beddafa42b1/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb22/7452591/6d9a1f9f9901/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb22/7452591/8f286f59e1f6/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb22/7452591/5be14b902d01/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb22/7452591/22fddc45ecce/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb22/7452591/f2e310ebd127/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb22/7452591/8888a1b2cefd/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb22/7452591/32ce76e0c8da/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb22/7452591/1e427df4dd1a/gr9.jpg

相似文献

1
BxPC-3-Derived Small Extracellular Vesicles Induce FOXP3+ Treg through ATM-AMPK-Sirtuins-Mediated FOXOs Nuclear Translocations.BxPC-3来源的小细胞外囊泡通过ATM-AMPK-沉默调节蛋白介导的FOXO核转位诱导FOXP3+调节性T细胞
iScience. 2020 Aug 21;23(8):101431. doi: 10.1016/j.isci.2020.101431. Epub 2020 Aug 2.
2
Embryonic Stem Cell Derived Small Extracellular Vesicles Modulate Regulatory T Cells to Protect against Ischemic Stroke.胚胎干细胞衍生的小细胞外囊泡调节调节性T细胞以预防缺血性中风。
ACS Nano. 2021 Apr 27;15(4):7370-7385. doi: 10.1021/acsnano.1c00672. Epub 2021 Mar 18.
3
Cancer-derived small extracellular vesicles: emerging biomarkers and therapies for pancreatic ductal adenocarcinoma diagnosis/prognosis and treatment.癌症来源的小细胞外囊泡：用于胰腺导管腺癌诊断/预后和治疗的新兴生物标志物和治疗方法。
J Nanobiotechnology. 2022 Oct 14;20(1):446. doi: 10.1186/s12951-022-01641-0.
4
Pancreatic cancer-derived small extracellular vesical Ezrin regulates macrophage polarization and promotes metastasis.胰腺癌来源的小细胞外囊泡Ezrin调节巨噬细胞极化并促进转移。
Am J Cancer Res. 2020 Jan 1;10(1):12-37. eCollection 2020.
5
Uniform 40-µm-pore diameter precision templated scaffolds promote a pro-healing host response by extracellular vesicle immune communication.均一孔径为 40 微米的精密模板支架通过细胞外囊泡免疫通讯促进有益的宿主反应。
J Tissue Eng Regen Med. 2021 Jan;15(1):24-36. doi: 10.1002/term.3160. Epub 2020 Dec 1.
6
Pancreatic Cancer Small Extracellular Vesicles (Exosomes): A Tale of Short- and Long-Distance Communication.胰腺癌小细胞外囊泡（外泌体）：短距离与长距离通讯的故事
Cancers (Basel). 2021 Sep 28;13(19):4844. doi: 10.3390/cancers13194844.
7
Integrated Genomic and Immunophenotypic Classification of Pancreatic Cancer Reveals Three Distinct Subtypes with Prognostic/Predictive Significance.胰腺癌的综合基因组和免疫表型分类揭示了具有预后/预测意义的三个不同亚型。
Clin Cancer Res. 2018 Sep 15;24(18):4444-4454. doi: 10.1158/1078-0432.CCR-17-3401. Epub 2018 Apr 16.
8
Small Extracellular Vesicles Harboring PD-L1 in Obstructive Sleep Apnea.小细胞外囊泡中含有阻塞性睡眠呼吸暂停相关的 PD-L1。
Int J Mol Sci. 2024 Mar 11;25(6):3208. doi: 10.3390/ijms25063208.
9
Protein Arginine Methylation Patterns in Plasma Small Extracellular Vesicles Are Altered in Patients with Early-Stage Pancreatic Ductal Adenocarcinoma.早期胰腺导管腺癌患者血浆小细胞外囊泡中的蛋白质精氨酸甲基化模式发生改变。
Cancers (Basel). 2024 Feb 3;16(3):654. doi: 10.3390/cancers16030654.
10
Single-cell RNA sequencing reveals compartmental remodeling of tumor-infiltrating immune cells induced by anti-CD47 targeting in pancreatic cancer.单细胞 RNA 测序揭示了抗 CD47 靶向治疗诱导的胰腺癌肿瘤浸润免疫细胞的区室重排。
J Hematol Oncol. 2019 Nov 27;12(1):124. doi: 10.1186/s13045-019-0822-6.

引用本文的文献

1
Therapeutic Potential of Polyphenols in Targeting Th17/Treg Balance for Intestinal Barrier Maintenance.多酚靶向Th17/Treg平衡维持肠道屏障的治疗潜力
Food Sci Nutr. 2025 Jun 7;13(6):e70400. doi: 10.1002/fsn3.70400. eCollection 2025 Jun.
2
Recent advances in potential enzymes and their therapeutic inhibitors for the treatment of Alzheimer's disease.用于治疗阿尔茨海默病的潜在酶及其治疗性抑制剂的最新进展。
Heliyon. 2024 Nov 28;10(23):e40756. doi: 10.1016/j.heliyon.2024.e40756. eCollection 2024 Dec 15.
3
Pancreatic cancer and exosomes: role in progression, diagnosis, monitoring, and treatment.

本文引用的文献

1
Inflammation and Pancreatic Cancer: Focus on Metabolism, Cytokines, and Immunity.炎症与胰腺癌：聚焦代谢、细胞因子与免疫。
Int J Mol Sci. 2019 Feb 5;20(3):676. doi: 10.3390/ijms20030676.
2
Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines.细胞外囊泡研究的最低限度信息2018（MISEV2018）：国际细胞外囊泡协会的立场声明及MISEV2014指南的更新
J Extracell Vesicles. 2018 Nov 23;7(1):1535750. doi: 10.1080/20013078.2018.1535750. eCollection 2018.
3
Cancer statistics, 2019.
胰腺癌与外泌体：在进展、诊断、监测及治疗中的作用
Front Oncol. 2023 May 23;13:1149551. doi: 10.3389/fonc.2023.1149551. eCollection 2023.
4
The role of DNA damage repair (DDR) system in response to immune checkpoint inhibitor (ICI) therapy.DNA 损伤修复（DDR）系统在免疫检查点抑制剂（ICI）治疗中的作用。
J Exp Clin Cancer Res. 2022 Sep 7;41(1):268. doi: 10.1186/s13046-022-02469-0.
5
Extracellular vesicles in pancreatic cancer progression and therapies.外泌体在胰腺癌进展和治疗中的作用。
Cell Death Dis. 2021 Oct 20;12(11):973. doi: 10.1038/s41419-021-04258-7.
6
The Heterogeneity of the Tumor Microenvironment as Essential Determinant of Development, Progression and Therapy Response of Pancreatic Cancer.肿瘤微环境的异质性作为胰腺癌发生、发展及治疗反应的关键决定因素
Cancers (Basel). 2021 Sep 30;13(19):4932. doi: 10.3390/cancers13194932.
7
Pancreatic Cancer Small Extracellular Vesicles (Exosomes): A Tale of Short- and Long-Distance Communication.胰腺癌小细胞外囊泡（外泌体）：短距离与长距离通讯的故事
Cancers (Basel). 2021 Sep 28;13(19):4844. doi: 10.3390/cancers13194844.
8
Small extracellular vesicle non-coding RNAs in pancreatic cancer: molecular mechanisms and clinical implications.小细胞外囊泡非编码 RNA 与胰腺癌：分子机制与临床意义。
J Hematol Oncol. 2021 Sep 8;14(1):141. doi: 10.1186/s13045-021-01149-4.
9
The Alterations in and the Role of the Th17/Treg Balance in Metabolic Diseases.代谢性疾病中 Th17/Treg 平衡的改变及其作用。
Front Immunol. 2021 Jul 12;12:678355. doi: 10.3389/fimmu.2021.678355. eCollection 2021.
10
Autophagy-Mediated Exosomes as Immunomodulators of Natural Killer Cells in Pancreatic Cancer Microenvironment.自噬介导的外泌体作为胰腺癌微环境中自然杀伤细胞的免疫调节剂
Front Oncol. 2021 Feb 19;10:622956. doi: 10.3389/fonc.2020.622956. eCollection 2020.
癌症统计数据，2019 年。
CA Cancer J Clin. 2019 Jan;69(1):7-34. doi: 10.3322/caac.21551. Epub 2019 Jan 8.
4
Regulatory T cells trigger effector T cell DNA damage and senescence caused by metabolic competition.调节性T细胞引发由代谢竞争导致的效应T细胞DNA损伤和衰老。
Nat Commun. 2018 Jan 16;9(1):249. doi: 10.1038/s41467-017-02689-5.
5
PDAC-derived exosomes enrich the microenvironment in MDSCs in a -dependent manner through a new calcium related axis.源自胰腺导管腺癌的外泌体通过一条新的钙相关轴以α-依赖的方式丰富髓系来源抑制细胞中的微环境。
Oncotarget. 2017 Sep 13;8(49):84928-84944. doi: 10.18632/oncotarget.20863. eCollection 2017 Oct 17.
6
Pancreatic cancer and associated exosomes.胰腺癌及其相关外泌体。
Cancer Biomark. 2017 Dec 6;20(4):357-367. doi: 10.3233/CBM-170258.
7
Combining Machine Learning and Nanofluidic Technology To Diagnose Pancreatic Cancer Using Exosomes.结合机器学习和纳流控技术，利用外泌体诊断胰腺癌。
ACS Nano. 2017 Nov 28;11(11):11182-11193. doi: 10.1021/acsnano.7b05503. Epub 2017 Oct 17.
8
ATM signals to AMPK to promote autophagy and positively regulate DNA damage in response to cadmium-induced ROS in mouse spermatocytes.在小鼠精母细胞中，共济失调毛细血管扩张症突变基因（ATM）向腺苷酸活化蛋白激酶（AMPK）发出信号以促进自噬，并对镉诱导的活性氧（ROS）作出反应，正向调节DNA损伤。
Environ Pollut. 2017 Dec;231(Pt 2):1560-1568. doi: 10.1016/j.envpol.2017.09.044. Epub 2017 Sep 28.
9
Pancreatic cancer: Exosomes for targeting KRAS in the treatment of pancreatic cancer.胰腺癌：用于治疗胰腺癌中靶向KRAS的外泌体
Nat Rev Gastroenterol Hepatol. 2017 Nov;14(11):636-638. doi: 10.1038/nrgastro.2017.113. Epub 2017 Sep 6.
10
Crosstalk between Regulatory T Cells and Tumor-Associated Dendritic Cells Negates Anti-tumor Immunity in Pancreatic Cancer.调节性T细胞与肿瘤相关树突状细胞之间的串扰削弱了胰腺癌的抗肿瘤免疫。
Cell Rep. 2017 Jul 18;20(3):558-571. doi: 10.1016/j.celrep.2017.06.062.