• 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

通过 JAK/STAT 信号通路靶向 CDCP1 增强宫颈癌中 CD8+T 细胞介导的细胞毒性。

Targeting CDCP1 boost CD8+ T cells-mediated cytotoxicity in cervical cancer via the JAK/STAT signaling pathway.

机构信息

Department of Obstetrics and Gynecology, Sun Yat-sen University First Affiliated Hospital, Guangzhou, Guangdong, China.

Guangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, Guangdong, China.

出版信息

J Immunother Cancer. 2024 Oct 24;12(10):e009416. doi: 10.1136/jitc-2024-009416.

DOI:10.1136/jitc-2024-009416
PMID:39455095
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11529519/
Abstract

BACKGROUND

Cervical cancer remains a global health challenge. The identification of new immunotherapeutic targets may provide a promising platform for advancing cervical cancer treatment.

OBJECTIVE

This study aims to investigate the role of CUB domain-containing protein 1 (CDCP1) in cervical cancer progression and evaluate its potential as a therapeutic target.

METHODS

We performed comprehensive analyses using patient cohorts and preclinical models to examine the association between CDCP1 expression and cervical cancer prognosis. Then in immunodeficient and immunocompetent mouse models, we further investigated the impact of CDCP1 on the tumor immune microenvironment, focusing on its effects on tumor-infiltrating T cells, including cytotoxic T lymphocytes (CTLs) and regulatory T cells (Tregs). Mechanistic studies were performed to elucidate the pathways involved in CDCP1-mediated immune modulation, in particular its interaction with the T cell receptor CD6 and the activation of the JAK-STAT signaling pathway.

RESULTS

Our results show that CDCP1 overexpression is associated with poor prognosis and T cell infliction in cervical cancer. Specifically, it affects the activity of CTLs and Tregs. Mechanistically, CDCP1 binds to CD6 and inhibits the JAK-STAT pathway of T cells. The study further demonstrates that targeting CDCP1 with the inhibitor 8-prenylnaringenin (8PN) effectively suppresses tumor growth in vivo and enhances antitumor immunity.

CONCLUSIONS

CDCP1 plays a critical role in cervical cancer progression by modulating the tumor immune microenvironment. Targeting CDCP1 offers a promising therapeutic strategy to improve the outcome of patients with cervical cancer.

摘要

背景

宫颈癌仍然是一个全球性的健康挑战。鉴定新的免疫治疗靶点可能为推进宫颈癌治疗提供一个有前景的平台。

目的

本研究旨在探讨 CUB 结构域包含蛋白 1（CDCP1）在宫颈癌进展中的作用，并评估其作为治疗靶点的潜力。

方法

我们使用患者队列和临床前模型进行了全面分析，以研究 CDCP1 表达与宫颈癌预后之间的关联。然后，在免疫缺陷和免疫功能正常的小鼠模型中，我们进一步研究了 CDCP1 对肿瘤免疫微环境的影响，重点关注其对肿瘤浸润性 T 细胞（包括细胞毒性 T 淋巴细胞（CTLs）和调节性 T 细胞（Tregs））的影响。进行了机制研究以阐明 CDCP1 介导的免疫调节涉及的途径，特别是其与 T 细胞受体 CD6 的相互作用和 JAK-STAT 信号通路的激活。

结果

我们的结果表明，CDCP1 过表达与宫颈癌的不良预后和 T 细胞浸润有关。具体而言，它影响 CTLs 和 Tregs 的活性。在机制上，CDCP1 与 CD6 结合并抑制 T 细胞的 JAK-STAT 通路。该研究进一步表明，用抑制剂 8-异戊烯基柚皮素（8PN）靶向 CDCP1 可有效抑制体内肿瘤生长并增强抗肿瘤免疫。

结论

CDCP1 通过调节肿瘤免疫微环境在宫颈癌进展中发挥关键作用。靶向 CDCP1 为改善宫颈癌患者的预后提供了有前途的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe47/11529519/228ab00574aa/jitc-12-10-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe47/11529519/d4542364d8d5/jitc-12-10-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe47/11529519/bad9cc131877/jitc-12-10-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe47/11529519/781d958c9036/jitc-12-10-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe47/11529519/6d0a90a2708a/jitc-12-10-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe47/11529519/e92b356f14a2/jitc-12-10-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe47/11529519/228ab00574aa/jitc-12-10-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe47/11529519/d4542364d8d5/jitc-12-10-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe47/11529519/bad9cc131877/jitc-12-10-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe47/11529519/781d958c9036/jitc-12-10-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe47/11529519/6d0a90a2708a/jitc-12-10-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe47/11529519/e92b356f14a2/jitc-12-10-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe47/11529519/228ab00574aa/jitc-12-10-g006.jpg

相似文献

1
Targeting CDCP1 boost CD8+ T cells-mediated cytotoxicity in cervical cancer via the JAK/STAT signaling pathway.通过 JAK/STAT 信号通路靶向 CDCP1 增强宫颈癌中 CD8+T 细胞介导的细胞毒性。
J Immunother Cancer. 2024 Oct 24;12(10):e009416. doi: 10.1136/jitc-2024-009416.
2
Delivery of Tapasin-modified CTL epitope peptide via cytoplasmic transduction peptide induces CTLs by JAK/STAT signaling pathway in vivo.通过细胞质转导肽递送 Tapasin 修饰的 CTL 表位肽通过 JAK/STAT 信号通路在体内诱导 CTL。
Acta Biochim Biophys Sin (Shanghai). 2018 Feb 1;50(2):181-190. doi: 10.1093/abbs/gmx133.
3
Inhibition of tumor metastasis: functional immune modulation of the CUB domain containing protein 1.抑制肿瘤转移：含 CUB 结构域蛋白 1 的功能免疫调节。
Mol Pharm. 2010 Feb 1;7(1):245-53. doi: 10.1021/mp900236t.
4
Elevated CDCP1 predicts poor patient outcome and mediates ovarian clear cell carcinoma by promoting tumor spheroid formation, cell migration and chemoresistance.CDCP1升高预示患者预后不良，并通过促进肿瘤球体形成、细胞迁移和化疗耐药介导卵巢透明细胞癌。
Oncogene. 2016 Jan 28;35(4):468-78. doi: 10.1038/onc.2015.101. Epub 2015 Apr 20.
5
A lipid-soluble extract of Pinellia pedatisecta Schott orchestrates intratumoral dendritic cell-driven immune activation through SOCS1 signaling in cervical cancer.半夏脂溶性提取物通过 SOCS1 信号调控宫颈癌内树突状细胞驱动的免疫激活。
J Ethnopharmacol. 2021 Mar 1;267:112837. doi: 10.1016/j.jep.2020.112837. Epub 2020 Apr 7.
6
Cell line and patient-derived xenograft models reveal elevated CDCP1 as a target in high-grade serous ovarian cancer.细胞系和患者来源的异种移植模型显示，在高级别浆液性卵巢癌中，CDCP1升高可作为一个靶点。
Br J Cancer. 2016 Feb 16;114(4):417-26. doi: 10.1038/bjc.2015.471. Epub 2016 Feb 4.
7
Targeting Jak/Stat pathway as a therapeutic strategy against SP/CD44+ tumorigenic cells in Akt/β-catenin-driven hepatocellular carcinoma.针对 Akt/β-catenin 驱动的肝癌中 SP/CD44+致瘤细胞的 Jak/Stat 通路作为一种治疗策略。
J Hepatol. 2020 Jan;72(1):104-118. doi: 10.1016/j.jhep.2019.08.035. Epub 2019 Sep 18.
8
Suppression of autophagy by CUB domain-containing protein 1 signaling is essential for anchorage-independent survival of lung cancer cells.CUB 结构域蛋白 1 信号抑制自噬对肺癌细胞锚定非依赖性存活至关重要。
Cancer Sci. 2013 Jul;104(7):865-70. doi: 10.1111/cas.12154. Epub 2013 Apr 19.
9
JAK/STAT Signaling and Cervical Cancer: From the Cell Surface to the Nucleus.JAK/STAT 信号通路与宫颈癌：从细胞表面到细胞核。
Genes (Basel). 2023 May 24;14(6):1141. doi: 10.3390/genes14061141.
10
Identification of CDCP1 as a hypoxia-inducible factor 2α (HIF-2α) target gene that is associated with survival in clear cell renal cell carcinoma patients.鉴定 CDCP1 为缺氧诱导因子 2α（HIF-2α）的靶基因，与透明细胞肾细胞癌患者的生存相关。
Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3483-8. doi: 10.1073/pnas.1222435110. Epub 2013 Feb 1.

引用本文的文献

1
Differential Role of CD318 in Tumor Immunity Affecting Prognosis in Colorectal Cancer Compared to Other Adenocarcinomas.与其他腺癌相比，CD318在影响结直肠癌预后的肿瘤免疫中的差异作用。
J Clin Med. 2025 Jul 19;14(14):5139. doi: 10.3390/jcm14145139.
2
Reverse-engineering the FLT3-PI3K/AKT axis to enhance TILs function and improve prognosis in ovarian and cervical cancers.逆向工程FLT3-PI3K/AKT轴以增强肿瘤浸润淋巴细胞功能并改善卵巢癌和宫颈癌的预后。
J Ovarian Res. 2025 Jan 25;18(1):14. doi: 10.1186/s13048-025-01592-8.

本文引用的文献

1
CD6 and Its Interacting Partners: Newcomers to the Block of Cancer Immunotherapies.CD6 及其相互作用伙伴：癌症免疫疗法的新成员。
Int J Mol Sci. 2023 Dec 15;24(24):17510. doi: 10.3390/ijms242417510.
2
CD6 triggers actomyosin cytoskeleton remodeling after binding to its receptor complex.CD6 与受体复合物结合后触发肌动球蛋白细胞骨架重塑。
J Leukoc Biol. 2024 Feb 23;115(3):450-462. doi: 10.1093/jleuko/qiad124.
3
Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer.JAK-STAT 信号通路的认知演变：自身免疫性疾病和癌症。
Signal Transduct Target Ther. 2023 May 19;8(1):204. doi: 10.1038/s41392-023-01468-7.
4
Inhibition of CDCP1 by 8-isopentenylnaringenin synergizes with EGFR inhibitors in lung cancer treatment.8-异戊烯基柚皮素抑制 CDCP1 与表皮生长因子受体抑制剂协同治疗肺癌。
Mol Oncol. 2023 Aug;17(8):1648-1665. doi: 10.1002/1878-0261.13429. Epub 2023 Apr 20.
5
Metastatic prostate cancer-derived extracellular vesicles facilitate osteoclastogenesis by transferring the CDCP1 protein.转移性前列腺癌衍生的细胞外囊泡通过转移 CDCP1 蛋白促进破骨细胞生成。
J Extracell Vesicles. 2023 Mar;12(3):e12312. doi: 10.1002/jev2.12312.
6
Human papillomavirus in cancer: Infection, disease transmission, and progress in vaccines.癌症中的人乳头瘤病毒：感染、疾病传播及疫苗进展。
J Infect Public Health. 2023 Apr;16(4):626-631. doi: 10.1016/j.jiph.2023.02.014. Epub 2023 Feb 21.
7
Theranostic Targeting of CUB Domain-Containing Protein 1 (CDCP1) in Multiple Subtypes of Bladder Cancer.CUB 结构域包含蛋白 1（CDCP1）在多种膀胱癌亚型中的治疗性靶向作用。
Clin Cancer Res. 2023 Apr 3;29(7):1232-1242. doi: 10.1158/1078-0432.CCR-22-1973.
8
CD6-mediated inhibition of T cell activation via modulation of Ras.CD6 通过调节 Ras 抑制 T 细胞活化。
Cell Commun Signal. 2022 Nov 21;20(1):184. doi: 10.1186/s12964-022-00998-x.
9
CUB Domain-Containing Protein 1 (CDCP1) is a rational target for the development of imaging tracers and antibody-drug conjugates for cancer detection and therapy.CUB 结构域包含蛋白 1（CDCP1）是开发成像示踪剂和用于癌症检测和治疗的抗体药物偶联物的合理靶标。
Theranostics. 2022 Oct 3;12(16):6915-6930. doi: 10.7150/thno.78171. eCollection 2022.
10
Dissecting the Single-Cell Transcriptome Network of Immune Environment Underlying Cervical Premalignant Lesion, Cervical Cancer and Metastatic Lymph Nodes.解析宫颈前病变、宫颈癌及转移淋巴结中免疫微环境的单细胞转录组网络。
Front Immunol. 2022 Jun 24;13:897366. doi: 10.3389/fimmu.2022.897366. eCollection 2022.