• 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

从检查点到检查点：DNA 损伤 ATR/Chk1 检查点信号引发 PD-L1 免疫检查点激活。

From checkpoint to checkpoint: DNA damage ATR/Chk1 checkpoint signalling elicits PD-L1 immune checkpoint activation.

机构信息

Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham & Women's Hospital, Harvard Medical School, Boston, MA, 02215, USA.

Gynecologic Medical Oncology Program, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02215, USA.

出版信息

Br J Cancer. 2018 Apr;118(7):933-935. doi: 10.1038/s41416-018-0017-x. Epub 2018 Mar 13.

DOI:10.1038/s41416-018-0017-x
PMID:29531322
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5931110/
Abstract

Multiple clinical studies have revealed a link between genomic instability and response to anti-PD-1/PD-L1 therapy in cancer management. A recent study has revealed an important role for the ATR/Chk1 DNA damage checkpoint in regulating PD-L1 expression, raising important clinical and translational questions for therapy selection and study design.

摘要

多项临床研究表明，基因组不稳定性与癌症治疗中抗 PD-1/PD-L1 治疗的反应之间存在关联。最近的一项研究揭示了 ATR/Chk1 DNA 损伤检查点在调节 PD-L1 表达中的重要作用，这为治疗选择和研究设计提出了重要的临床和转化问题。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0917/5931110/ff110cce054e/41416_2018_17_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0917/5931110/ff110cce054e/41416_2018_17_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0917/5931110/ff110cce054e/41416_2018_17_Fig1_HTML.jpg

相似文献

1
From checkpoint to checkpoint: DNA damage ATR/Chk1 checkpoint signalling elicits PD-L1 immune checkpoint activation.从检查点到检查点：DNA 损伤 ATR/Chk1 检查点信号引发 PD-L1 免疫检查点激活。
Br J Cancer. 2018 Apr;118(7):933-935. doi: 10.1038/s41416-018-0017-x. Epub 2018 Mar 13.
2
The ATM-Chk2 and ATR-Chk1 pathways in DNA damage signaling and cancer.ATM-Chk2 和 ATR-Chk1 通路在 DNA 损伤信号转导和癌症中的作用。
Adv Cancer Res. 2010;108:73-112. doi: 10.1016/B978-0-12-380888-2.00003-0.
3
UV-induced G2 checkpoint depends on p38 MAPK and minimal activation of ATR-Chk1 pathway.紫外线诱导的 G2 检验点依赖于 p38MAPK 和 ATR-Chk1 通路的最小激活。
J Cell Sci. 2013 May 1;126(Pt 9):1923-30. doi: 10.1242/jcs.118265. Epub 2013 Feb 27.
4
Somatic mutations in the DNA damage-response genes ATR and CHK1 in sporadic stomach tumors with microsatellite instability.散发性微卫星不稳定胃肿瘤中DNA损伤反应基因ATR和CHK1的体细胞突变
Cancer Res. 2001 Nov 1;61(21):7727-30.
5
Chk1- and claspin-dependent but ATR/ATM- and Rad17-independent DNA replication checkpoint response in HeLa cells.HeLa细胞中依赖Chk1和claspin但不依赖ATR/ATM和Rad17的DNA复制检查点反应
Cancer Res. 2006 Sep 1;66(17):8672-9. doi: 10.1158/0008-5472.CAN-05-4443.
6
Ultrasound activates ataxia telangiectasia mutated- and rad3-related (ATR)-checkpoint kinase 1 (Chk1) pathway in human leukemia Jurkat cells.超声激活人白血病 Jurkat 细胞中的共济失调毛细血管扩张突变和 rad3 相关（ATR）检查点激酶 1（Chk1）通路。
Ultrason Sonochem. 2012 Nov;19(6):1246-51. doi: 10.1016/j.ultsonch.2012.04.003. Epub 2012 Apr 19.
7
Rapid PIKK-dependent release of Chk1 from chromatin promotes the DNA-damage checkpoint response.依赖PIKK的Chk1从染色质上的快速释放促进了DNA损伤检查点反应。
Curr Biol. 2006 Jan 24;16(2):150-9. doi: 10.1016/j.cub.2005.11.066. Epub 2005 Dec 15.
8
Interaction between Rad9-Hus1-Rad1 and TopBP1 activates ATR-ATRIP and promotes TopBP1 recruitment to sites of UV-damage.Rad9-Hus1-Rad1与TopBP1之间的相互作用激活了ATR-ATRIP，并促进TopBP1募集到紫外线损伤位点。
DNA Repair (Amst). 2014 Sep;21:1-11. doi: 10.1016/j.dnarep.2014.05.001. Epub 2014 May 27.
9
Mutations in the ataxia telangiectasia and rad3-related-checkpoint kinase 1 DNA damage response axis in colon cancers.结肠癌中共济失调毛细血管扩张症和Rad3相关检查点激酶1 DNA损伤反应轴的突变
Genes Chromosomes Cancer. 2007 Dec;46(12):1061-8. doi: 10.1002/gcc.20486.
10
Rad17 phosphorylation is required for claspin recruitment and Chk1 activation in response to replication stress.Rad17磷酸化是响应复制应激时募集Claspin和激活Chk1所必需的。
Mol Cell. 2006 Aug 4;23(3):331-41. doi: 10.1016/j.molcel.2006.06.022.

引用本文的文献

1
Elucidating DNA Damage-Dependent Immune System Activation.阐明DNA损伤依赖性免疫系统激活。
Int J Mol Sci. 2025 Jun 18;26(12):5849. doi: 10.3390/ijms26125849.
2
Senescence-associated secretory phenotype in lung cancer: remodeling the tumor microenvironment for metastasis and immune suppression.肺癌中的衰老相关分泌表型：重塑肿瘤微环境以促进转移和免疫抑制。
Front Oncol. 2025 May 29;15:1605085. doi: 10.3389/fonc.2025.1605085. eCollection 2025.
3
Early Immune Checkpoint Inhibitor Administration Increases the Risk of Radiation-Induced Pneumonitis in Patients with Stage III Unresectable NSCLC Undergoing Chemoradiotherapy.

本文引用的文献

1
DNA double-strand break repair pathway regulates PD-L1 expression in cancer cells.DNA 双链断裂修复途径调控癌细胞中 PD-L1 的表达。
Nat Commun. 2017 Nov 24;8(1):1751. doi: 10.1038/s41467-017-01883-9.
2
EZH2 promotes degradation of stalled replication forks by recruiting MUS81 through histone H3 trimethylation.EZH2 通过招募 MUS81 并通过组蛋白 H3 三甲基化促进停滞复制叉的降解。
Nat Cell Biol. 2017 Nov;19(11):1371-1378. doi: 10.1038/ncb3626. Epub 2017 Oct 16.
3
DNA Damage and Repair Biomarkers of Immunotherapy Response.免疫治疗反应的DNA损伤与修复生物标志物
在接受放化疗的 III 期不可切除非小细胞肺癌患者中，早期给予免疫检查点抑制剂会增加放射性肺炎的风险。
Cancers (Basel). 2025 May 20;17(10):1711. doi: 10.3390/cancers17101711.
4
The double life of a chemotherapy drug: Immunomodulatory functions of gemcitabine in cancer.化疗药物的双重生活：吉西他滨在癌症中的免疫调节功能。
Cancer Med. 2024 May;13(10):e7287. doi: 10.1002/cam4.7287.
5
Exceptional synergistic response of PARP inhibitor and immune checkpoint inhibitor in esophageal adenocarcinoma with a germline BRCA2 mutation: a case report.PARP抑制剂与免疫检查点抑制剂在伴有胚系BRCA2突变的食管腺癌中的卓越协同反应：一例报告
Ther Adv Med Oncol. 2024 Mar 30;16:17588359241242406. doi: 10.1177/17588359241242406. eCollection 2024.
6
Undifferentiated Carcinoma with Osteoclast-like Giant Cells of the Pancreas: Molecular Genetic Analysis of 13 Cases.胰腺未分化癌伴破骨样巨细胞：13 例的分子遗传学分析。
Int J Mol Sci. 2024 Mar 14;25(6):3285. doi: 10.3390/ijms25063285.
7
Promises of Protein Kinase Inhibitors in Recalcitrant Small-Cell Lung Cancer: Recent Scenario and Future Possibilities.蛋白激酶抑制剂在难治性小细胞肺癌中的前景：近期情况与未来可能性
Cancers (Basel). 2024 Feb 27;16(5):963. doi: 10.3390/cancers16050963.
8
Key Proteins of Replication Stress Response and Cell Cycle Control as Cancer Therapy Targets.作为癌症治疗靶点的复制应激反应和细胞周期调控关键蛋白。
Int J Mol Sci. 2024 Jan 19;25(2):1263. doi: 10.3390/ijms25021263.
9
Inhibitors of phosphoinositide 3-kinase (PI3K) and phosphoinositide 3-kinase-related protein kinase family (PIKK).磷酸肌醇 3-激酶 (PI3K) 和磷酸肌醇 3-激酶相关蛋白激酶家族 (PIKK) 的抑制剂。
J Enzyme Inhib Med Chem. 2023 Dec;38(1):2237209. doi: 10.1080/14756366.2023.2237209.
10
DNA Damage Response-Related Proteins Are Prognostic for Outcome in Both Adult and Pediatric Acute Myelogenous Leukemia Patients: Samples from Adults and from Children Enrolled in a Children's Oncology Group Study.DNA 损伤反应相关蛋白对成人和儿童急性髓细胞白血病患者的预后均有意义：该研究样本来自成年人和儿童肿瘤组研究中的儿童。
Int J Mol Sci. 2023 Mar 20;24(6):5898. doi: 10.3390/ijms24065898.
Cancer Discov. 2017 Jul;7(7):675-693. doi: 10.1158/2159-8290.CD-17-0226. Epub 2017 Jun 19.
4
ATR inhibition disrupts rewired homologous recombination and fork protection pathways in PARP inhibitor-resistant BRCA-deficient cancer cells.ATR抑制作用会破坏PARP抑制剂耐药的BRCA缺陷癌细胞中重新连接的同源重组和叉保护途径。
Genes Dev. 2017 Feb 1;31(3):318-332. doi: 10.1101/gad.290957.116. Epub 2017 Feb 27.
5
Activation of STING-Dependent Innate Immune Signaling By S-Phase-Specific DNA Damage in Breast Cancer.乳腺癌中S期特异性DNA损伤对STING依赖性先天免疫信号的激活
J Natl Cancer Inst. 2016 Oct 5;109(1). doi: 10.1093/jnci/djw199. Print 2017 Jan.
6
Replication fork stability confers chemoresistance in BRCA-deficient cells.复制叉稳定性赋予BRCA缺陷细胞化学抗性。
Nature. 2016 Jul 21;535(7612):382-7. doi: 10.1038/nature18325.
7
Immune Checkpoint Inhibition for Hypermutant Glioblastoma Multiforme Resulting From Germline Biallelic Mismatch Repair Deficiency.免疫检查点抑制治疗胚系双等位基因错配修复缺陷所致超突变胶质母细胞瘤多形性。
J Clin Oncol. 2016 Jul 1;34(19):2206-11. doi: 10.1200/JCO.2016.66.6552. Epub 2016 Mar 21.
8
Association and prognostic significance of BRCA1/2-mutation status with neoantigen load, number of tumor-infiltrating lymphocytes and expression of PD-1/PD-L1 in high grade serous ovarian cancer.BRCA1/2基因突变状态与高级别浆液性卵巢癌新抗原负荷、肿瘤浸润淋巴细胞数量及PD-1/PD-L1表达的相关性及预后意义
Oncotarget. 2016 Mar 22;7(12):13587-98. doi: 10.18632/oncotarget.7277.
9
Homologous Recombination Deficiency: Exploiting the Fundamental Vulnerability of Ovarian Cancer.同源重组缺陷：利用卵巢癌的根本脆弱性
Cancer Discov. 2015 Nov;5(11):1137-54. doi: 10.1158/2159-8290.CD-15-0714. Epub 2015 Oct 13.
10
Association of Polymerase e-Mutated and Microsatellite-Instable Endometrial Cancers With Neoantigen Load, Number of Tumor-Infiltrating Lymphocytes, and Expression of PD-1 and PD-L1.聚合酶 e 突变和微卫星不稳定型子宫内膜癌与新抗原负荷、肿瘤浸润淋巴细胞数量以及 PD-1 和 PD-L1 表达的关联。
JAMA Oncol. 2015 Dec;1(9):1319-23. doi: 10.1001/jamaoncol.2015.2151.