CCL22 as an independent prognostic factor in endometrial cancer patients

IF 5 2区 医学 Q2 Medicine Translational Oncology Pub Date : 2024-09-03 DOI:10.1016/j.tranon.2024.102116
{"title":"CCL22 as an independent prognostic factor in endometrial cancer patients","authors":"","doi":"10.1016/j.tranon.2024.102116","DOIUrl":null,"url":null,"abstract":"<div><h3>Objectives</h3><p>The chemokine CCL22 is recognized for recruiting immunosuppressive regulatory T-cells (Treg) that contribute to disease progression in various tumor entities helping them to evade the host immune response. Our study aims to identify the expressing cell types and to evaluate the prognostic significance of CCL22 secretion and its association with Treg invasion in endometrial cancer (EC), an immunogenic cancer.</p></div><div><h3>Methods</h3><p>Specimens from 275 patients with EC and 28 healthy controls were screened immunohistochemically for CCL22. Immunofluorescence double-staining for CCL22 and different immune cell markers was performed. In vitro regulation of CCL22-expression was examined in EC cell lines (Ishikawa+, RL95–2) and human PBMCs in coculture settings via qPCR and ELISA.</p></div><div><h3>Results</h3><p>Elevated CCL22 staining in tumor cells and CCL22-positive M1-macrophages in tumordistant areas were significantly associated with increased overall survival (OS). Conversely, high, secretory-appearing staining in the peritumoral and intratumoral stroma correlated with reduced OS. Although the analysis of the in vitro coculture model of epithelial tumor- and immune cells revealed PBMCs as the primary source of CCL22, we could confirm expression of the chemokine also in the EC epithelial cells.</p></div><div><h3>Conclusion</h3><p>Our study suggests that CCL22 in EC is associated with OS, dependent on its location and the cell type producing it. Intracellular upregulation and extracellular secretion must be considered separately when investigating CCL22 expressing cell types in EC. These results may provide evidence for CCL22-mediated Treg recruitment in EC as a potential future therapeutic target.</p></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0000,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1936523324002432/pdfft?md5=b29186b49bb5434ee8561a1198172e61&pid=1-s2.0-S1936523324002432-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational Oncology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1936523324002432","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0

Abstract

Objectives

The chemokine CCL22 is recognized for recruiting immunosuppressive regulatory T-cells (Treg) that contribute to disease progression in various tumor entities helping them to evade the host immune response. Our study aims to identify the expressing cell types and to evaluate the prognostic significance of CCL22 secretion and its association with Treg invasion in endometrial cancer (EC), an immunogenic cancer.

Methods

Specimens from 275 patients with EC and 28 healthy controls were screened immunohistochemically for CCL22. Immunofluorescence double-staining for CCL22 and different immune cell markers was performed. In vitro regulation of CCL22-expression was examined in EC cell lines (Ishikawa+, RL95–2) and human PBMCs in coculture settings via qPCR and ELISA.

Results

Elevated CCL22 staining in tumor cells and CCL22-positive M1-macrophages in tumordistant areas were significantly associated with increased overall survival (OS). Conversely, high, secretory-appearing staining in the peritumoral and intratumoral stroma correlated with reduced OS. Although the analysis of the in vitro coculture model of epithelial tumor- and immune cells revealed PBMCs as the primary source of CCL22, we could confirm expression of the chemokine also in the EC epithelial cells.

Conclusion

Our study suggests that CCL22 in EC is associated with OS, dependent on its location and the cell type producing it. Intracellular upregulation and extracellular secretion must be considered separately when investigating CCL22 expressing cell types in EC. These results may provide evidence for CCL22-mediated Treg recruitment in EC as a potential future therapeutic target.

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
作为子宫内膜癌患者独立预后因素的 CCL22
目的趋化因子CCL22被认为能招募免疫抑制性调节性T细胞(Treg),从而促进各种肿瘤实体的疾病进展,帮助它们逃避宿主免疫反应。我们的研究旨在确定表达CCL22的细胞类型,并评估CCL22分泌的预后意义及其与免疫原性癌症子宫内膜癌(EC)中Treg入侵的关联。对 CCL22 和不同的免疫细胞标记物进行免疫荧光双重染色。通过 qPCR 和 ELISA 检测了体外调节 CCL22 表达的 EC 细胞系(石川+、RL95-2)和共培养环境中的人 PBMC。相反,瘤周和瘤内基质中的高分泌性染色与 OS 下降相关。尽管对肿瘤上皮细胞和免疫细胞体外共培养模型的分析表明,PBMCs 是 CCL22 的主要来源,但我们可以证实 EC 上皮细胞中也有该趋化因子的表达。在研究 EC 中表达 CCL22 的细胞类型时,必须分别考虑细胞内上调和细胞外分泌。这些研究结果可能为CCL22介导的Treg在EC中的招募提供了证据,是未来潜在的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
CiteScore
8.40
自引率
2.00%
发文量
314
审稿时长
54 days
期刊介绍: Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.
期刊最新文献
Cancer is not a guest Universal CAR cell therapy: Challenges and expanding applications High circulating activin A plasma levels are associated with tumour stage and poor survival in treatment-naive lung squamous cell cancer patients Proteomic and metabolomic profiles of plasma-derived Extracellular Vesicles differentiate melanoma patients from healthy controls First in human intraarterial delivery of tislelizumab for the treatment of pMMR locally advanced rectal cancer: A single-arm, open label, phase II clinical trial
×
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