抗CSF-1R疗法的纤维化反应会加剧胶质母细胞瘤的复发

IF 48.8 1区 医学 Q1 CELL BIOLOGY Cancer Cell Pub Date : 2024-09-09 DOI:10.1016/j.ccell.2024.08.012
Spencer S. Watson, Anoek Zomer, Nadine Fournier, Joao Lourenco, Manfredo Quadroni, Agnieszka Chryplewicz, Sina Nassiri, Pauline Aubel, Simona Avanthay, Davide Croci, Erik Abels, Marike L.D. Broekman, Douglas Hanahan, Jason T. Huse, Roy T. Daniel, Monika E. Hegi, Krisztian Homicsko, Giulia Cossu, Andreas F. Hottinger, Johanna A. Joyce
{"title":"抗CSF-1R疗法的纤维化反应会加剧胶质母细胞瘤的复发","authors":"Spencer S. Watson, Anoek Zomer, Nadine Fournier, Joao Lourenco, Manfredo Quadroni, Agnieszka Chryplewicz, Sina Nassiri, Pauline Aubel, Simona Avanthay, Davide Croci, Erik Abels, Marike L.D. Broekman, Douglas Hanahan, Jason T. Huse, Roy T. Daniel, Monika E. Hegi, Krisztian Homicsko, Giulia Cossu, Andreas F. Hottinger, Johanna A. Joyce","doi":"10.1016/j.ccell.2024.08.012","DOIUrl":null,"url":null,"abstract":"<p>Glioblastoma recurrence is currently inevitable despite extensive standard-of-care treatment. In preclinical studies, an alternative strategy of targeting tumor-associated macrophages and microglia through CSF-1R inhibition was previously found to regress established tumors and significantly increase overall survival. However, recurrences developed in ∼50% of mice in long-term studies, which were consistently associated with fibrotic scars. This fibrotic response is observed following multiple anti-glioma therapies in different preclinical models herein and in patient recurrence samples. Multi-omics analyses of the post-treatment tumor microenvironment identified fibrotic areas as pro-tumor survival niches that encapsulated surviving glioma cells, promoted dormancy, and inhibited immune surveillance. The fibrotic treatment response was mediated by perivascular-derived fibroblast-like cells via activation by transforming growth factor β (TGF-β) signaling and neuroinflammation. Concordantly, combinatorial inhibition of these pathways inhibited treatment-associated fibrosis, and significantly improved survival in preclinical trials of anti-colony-stimulating factor-1 receptor (CSF-1R) therapy.</p>","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":null,"pages":null},"PeriodicalIF":48.8000,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Fibrotic response to anti-CSF-1R therapy potentiates glioblastoma recurrence\",\"authors\":\"Spencer S. Watson, Anoek Zomer, Nadine Fournier, Joao Lourenco, Manfredo Quadroni, Agnieszka Chryplewicz, Sina Nassiri, Pauline Aubel, Simona Avanthay, Davide Croci, Erik Abels, Marike L.D. Broekman, Douglas Hanahan, Jason T. Huse, Roy T. Daniel, Monika E. Hegi, Krisztian Homicsko, Giulia Cossu, Andreas F. Hottinger, Johanna A. Joyce\",\"doi\":\"10.1016/j.ccell.2024.08.012\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Glioblastoma recurrence is currently inevitable despite extensive standard-of-care treatment. In preclinical studies, an alternative strategy of targeting tumor-associated macrophages and microglia through CSF-1R inhibition was previously found to regress established tumors and significantly increase overall survival. However, recurrences developed in ∼50% of mice in long-term studies, which were consistently associated with fibrotic scars. This fibrotic response is observed following multiple anti-glioma therapies in different preclinical models herein and in patient recurrence samples. Multi-omics analyses of the post-treatment tumor microenvironment identified fibrotic areas as pro-tumor survival niches that encapsulated surviving glioma cells, promoted dormancy, and inhibited immune surveillance. The fibrotic treatment response was mediated by perivascular-derived fibroblast-like cells via activation by transforming growth factor β (TGF-β) signaling and neuroinflammation. Concordantly, combinatorial inhibition of these pathways inhibited treatment-associated fibrosis, and significantly improved survival in preclinical trials of anti-colony-stimulating factor-1 receptor (CSF-1R) therapy.</p>\",\"PeriodicalId\":9670,\"journal\":{\"name\":\"Cancer Cell\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":48.8000,\"publicationDate\":\"2024-09-09\",\"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.2024.08.012\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Cell","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ccell.2024.08.012","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

摘要

尽管进行了广泛的标准治疗,但目前胶质母细胞瘤的复发仍不可避免。在临床前研究中,一种通过抑制 CSF-1R 靶向肿瘤相关巨噬细胞和小胶质细胞的替代策略被发现可以使已形成的肿瘤消退,并显著提高总生存率。然而,在长期研究中,有 50% 的小鼠出现了复发,而且始终伴有纤维化疤痕。在不同的临床前模型和患者复发样本中,都观察到了多种抗胶质瘤疗法后的纤维化反应。对治疗后肿瘤微环境的多组学分析发现,纤维化区域是有利于肿瘤存活的龛位,可包裹存活的胶质瘤细胞、促进休眠并抑制免疫监视。纤维化治疗反应是由血管周围衍生的成纤维细胞样细胞通过转化生长因子β(TGF-β)信号和神经炎症激活介导的。同时,对这些通路的联合抑制可抑制治疗相关的纤维化,并在抗集落刺激因子-1受体(CSF-1R)疗法的临床前试验中显著提高存活率。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

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
Fibrotic response to anti-CSF-1R therapy potentiates glioblastoma recurrence

Glioblastoma recurrence is currently inevitable despite extensive standard-of-care treatment. In preclinical studies, an alternative strategy of targeting tumor-associated macrophages and microglia through CSF-1R inhibition was previously found to regress established tumors and significantly increase overall survival. However, recurrences developed in ∼50% of mice in long-term studies, which were consistently associated with fibrotic scars. This fibrotic response is observed following multiple anti-glioma therapies in different preclinical models herein and in patient recurrence samples. Multi-omics analyses of the post-treatment tumor microenvironment identified fibrotic areas as pro-tumor survival niches that encapsulated surviving glioma cells, promoted dormancy, and inhibited immune surveillance. The fibrotic treatment response was mediated by perivascular-derived fibroblast-like cells via activation by transforming growth factor β (TGF-β) signaling and neuroinflammation. Concordantly, combinatorial inhibition of these pathways inhibited treatment-associated fibrosis, and significantly improved survival in preclinical trials of anti-colony-stimulating factor-1 receptor (CSF-1R) therapy.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
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.
期刊最新文献
Itaconate transporter SLC13A3 impairs tumor immunity via endowing ferroptosis resistance Targeting the immune privilege of tumor-initiating cells to enhance cancer immunotherapy Intratumoral vidutolimod in combination with PD-1 blockade in locoregionally advanced melanoma Neoadjuvant vidutolimod and nivolumab in high-risk resectable melanoma: A prospective phase II trial Fertility outcomes post immune checkpoint inhibitor exposure
×
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