Selective depletion of CCR8+Treg cells enhances anti-tumor immunity of cytotoxic T cells in lung cancer via dendritic cells.

IF 21 1区 医学 Q1 ONCOLOGY Journal of Thoracic Oncology Pub Date : 2025-03-06 DOI:10.1016/j.jtho.2025.02.029
Peixin Chen, Haowei Wang, Zhuoran Tang, Jinpeng Shi, Lei Cheng, Chao Zhao, Xuefei Li, Caicun Zhou
{"title":"Selective depletion of CCR8+Treg cells enhances anti-tumor immunity of cytotoxic T cells in lung cancer via dendritic cells.","authors":"Peixin Chen, Haowei Wang, Zhuoran Tang, Jinpeng Shi, Lei Cheng, Chao Zhao, Xuefei Li, Caicun Zhou","doi":"10.1016/j.jtho.2025.02.029","DOIUrl":null,"url":null,"abstract":"<p><p>Accumulation of regulatory T (Treg) cells, an immunosuppressive population, limits the efficacy of immunotherapy in non-small cell lung cancer (NSCLC). C-C Motif Chemokine Receptor 8 (CCR8) is selectively expressed in tumor-infiltrating Treg cells and, thus considered an ideal target. Across four NSCLC-bearing mice models, the combination of CCR8 antibody and programmed cell death protein-1 (PD1) inhibitor significantly reduced tumor growth without obvious mouse body weight drops and systemic cytokine storm. The single-cell RNA and T-cell receptor sequencing analysis demonstrated that anti-CCR8 therapy synergizes with PD1 blockade by remodeling the tumor microenvironment and disrupting CCR8+Treg - CCL5+ dendritic cells (DC) interaction. Mechanistically, therapeutic depletion of CCR8+Treg cells combined with PD1 inhibitor extremely increased interleukin-12 secretion by the JAK-STAT pathway activation on CCL5+ DCs, thereby promoting cytotoxic activity of CD8+ T cells. The therapeutic potential of the CCR8 antibody LM-108 in combination with immunotherapy was observed in clinical patients with advanced NSCLC. Overall, CCR8 expression on tumor-infiltrating Treg cells is correlated with immunosuppressive function on DCs and CD8+ T cells, thus impeding anti-tumor immunity.</p>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":" ","pages":""},"PeriodicalIF":21.0000,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Thoracic Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jtho.2025.02.029","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Accumulation of regulatory T (Treg) cells, an immunosuppressive population, limits the efficacy of immunotherapy in non-small cell lung cancer (NSCLC). C-C Motif Chemokine Receptor 8 (CCR8) is selectively expressed in tumor-infiltrating Treg cells and, thus considered an ideal target. Across four NSCLC-bearing mice models, the combination of CCR8 antibody and programmed cell death protein-1 (PD1) inhibitor significantly reduced tumor growth without obvious mouse body weight drops and systemic cytokine storm. The single-cell RNA and T-cell receptor sequencing analysis demonstrated that anti-CCR8 therapy synergizes with PD1 blockade by remodeling the tumor microenvironment and disrupting CCR8+Treg - CCL5+ dendritic cells (DC) interaction. Mechanistically, therapeutic depletion of CCR8+Treg cells combined with PD1 inhibitor extremely increased interleukin-12 secretion by the JAK-STAT pathway activation on CCL5+ DCs, thereby promoting cytotoxic activity of CD8+ T cells. The therapeutic potential of the CCR8 antibody LM-108 in combination with immunotherapy was observed in clinical patients with advanced NSCLC. Overall, CCR8 expression on tumor-infiltrating Treg cells is correlated with immunosuppressive function on DCs and CD8+ T cells, thus impeding anti-tumor immunity.

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
求助全文
约1分钟内获得全文 去求助
来源期刊
Journal of Thoracic Oncology
Journal of Thoracic Oncology 医学-呼吸系统
CiteScore
36.00
自引率
3.90%
发文量
1406
审稿时长
13 days
期刊介绍: Journal of Thoracic Oncology (JTO), the official journal of the International Association for the Study of Lung Cancer,is the primary educational and informational publication for topics relevant to the prevention, detection, diagnosis, and treatment of all thoracic malignancies.The readship includes epidemiologists, medical oncologists, radiation oncologists, thoracic surgeons, pulmonologists, radiologists, pathologists, nuclear medicine physicians, and research scientists with a special interest in thoracic oncology.
期刊最新文献
Gut Microbiota in Advanced Non-small-cell Lung Cancer Receiving Chemo-immunotherapy: An Ancillary Biomarker Study from the Phase III trial JCOG2007 (NIPPON). Selective depletion of CCR8+Treg cells enhances anti-tumor immunity of cytotoxic T cells in lung cancer via dendritic cells. Erratum In this issue Editorial Board
×
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