Subclonal immune evasion in non-small cell lung cancer

IF 48.8 1区 医学 Q1 CELL BIOLOGY
Krijn K. Dijkstra, Roberto Vendramin, Despoina Karagianni, Maartje Witsen, Felipe Gálvez-Cancino, Mark S. Hill, Kane A. Foster, Vittorio Barbè, Mihaela Angelova, Robert E. Hynds, David R. Pearce, Carlos Martínez-Ruiz, James R.M. Black, Ariana Huebner, Oriol Pich, Andrew Rowan, Marcellus Augustine, Clare Puttick, David A. Moore, Lydia L. Liu, Charles Swanton
{"title":"Subclonal immune evasion in non-small cell lung cancer","authors":"Krijn K. Dijkstra, Roberto Vendramin, Despoina Karagianni, Maartje Witsen, Felipe Gálvez-Cancino, Mark S. Hill, Kane A. Foster, Vittorio Barbè, Mihaela Angelova, Robert E. Hynds, David R. Pearce, Carlos Martínez-Ruiz, James R.M. Black, Ariana Huebner, Oriol Pich, Andrew Rowan, Marcellus Augustine, Clare Puttick, David A. Moore, Lydia L. Liu, Charles Swanton","doi":"10.1016/j.ccell.2025.06.012","DOIUrl":null,"url":null,"abstract":"Cancers rarely respond completely to immunotherapy. While tumors consist of multiple genetically distinct clones, whether this affects the potential for immune escape remains unclear due to an inability to isolate and propagate individual subclones from human cancers. Here, we leverage the multi-region TRACERx lung cancer evolution study to generate a patient-derived organoid – T cell co-culture platform that allows the functional analysis of subclonal immune escape at single clone resolution. We establish organoid lines from 11 separate tumor regions from three patients, followed by isolation of 81 individual clonal sublines. Co-culture with tumor infiltrating lymphocytes (TIL) or natural killer (NK) cells reveals cancer-intrinsic and subclonal immune escape in all 3 patients. Immune evading subclones represent genetically distinct lineages with a unique evolutionary history. This indicates that immune evading and non-evading subclones can be isolated from the same tumor, suggesting that subclonal tumor evolution directly affects immune escape.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"7 1","pages":""},"PeriodicalIF":48.8000,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Cell","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ccell.2025.06.012","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Cancers rarely respond completely to immunotherapy. While tumors consist of multiple genetically distinct clones, whether this affects the potential for immune escape remains unclear due to an inability to isolate and propagate individual subclones from human cancers. Here, we leverage the multi-region TRACERx lung cancer evolution study to generate a patient-derived organoid – T cell co-culture platform that allows the functional analysis of subclonal immune escape at single clone resolution. We establish organoid lines from 11 separate tumor regions from three patients, followed by isolation of 81 individual clonal sublines. Co-culture with tumor infiltrating lymphocytes (TIL) or natural killer (NK) cells reveals cancer-intrinsic and subclonal immune escape in all 3 patients. Immune evading subclones represent genetically distinct lineages with a unique evolutionary history. This indicates that immune evading and non-evading subclones can be isolated from the same tumor, suggesting that subclonal tumor evolution directly affects immune escape.

Abstract Image

非小细胞肺癌的亚克隆免疫逃避
癌症很少对免疫疗法有完全的反应。虽然肿瘤由多个遗传上不同的克隆组成,但由于无法从人类癌症中分离和繁殖单个亚克隆,这是否会影响免疫逃逸的潜力仍不清楚。在这里,我们利用多区域TRACERx肺癌进化研究来生成一个患者来源的类器官- T细胞共培养平台,允许在单克隆分辨率下进行亚克隆免疫逃逸的功能分析。我们从3例患者的11个不同肿瘤区域建立了类器官系,随后分离了81个单个克隆亚系。与肿瘤浸润淋巴细胞(TIL)或自然杀伤细胞(NK)共培养显示所有3例患者的肿瘤固有和亚克隆免疫逃逸。免疫逃避亚克隆代表了具有独特进化历史的遗传上不同的谱系。这表明在同一肿瘤中可以分离出免疫逃避亚克隆和非逃避亚克隆,提示肿瘤亚克隆进化直接影响免疫逃避。
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 求助全文
来源期刊
Cancer Cell
Cancer Cell 医学-肿瘤学
CiteScore
55.20
自引率
1.20%
发文量
179
审稿时长
4-8 weeks
期刊介绍: Cancer Cell is a journal that focuses on promoting major advances in cancer research and oncology. The primary criteria for considering manuscripts are as follows: Major advances: Manuscripts should provide significant advancements in answering important questions related to naturally occurring cancers. Translational research: The journal welcomes translational research, which involves the application of basic scientific findings to human health and clinical practice. Clinical investigations: Cancer Cell is interested in publishing clinical investigations that contribute to establishing new paradigms in the treatment, diagnosis, or prevention of cancers. Insights into cancer biology: The journal values clinical investigations that provide important insights into cancer biology beyond what has been revealed by preclinical studies. Mechanism-based proof-of-principle studies: Cancer Cell encourages the publication of mechanism-based proof-of-principle clinical studies, which demonstrate the feasibility of a specific therapeutic approach or diagnostic test.
×
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
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
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 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信