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2 型固有淋巴细胞不参与小鼠膀胱癌的发生发展。

Type 2 innate lymphoid cells are not involved in mouse bladder tumor development.

机构信息

Urology Research Unit and Urology Biobank, Department of Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.

出版信息

Front Immunol. 2024 Jan 12;14:1335326. doi: 10.3389/fimmu.2023.1335326. eCollection 2023.

DOI:10.3389/fimmu.2023.1335326
PMID:38283350
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10820705/
Abstract

Therapies for bladder cancer patients are limited by side effects and failures, highlighting the need for novel targets to improve disease management. Given the emerging evidence highlighting the key role of innate lymphoid cell subsets, especially type 2 innate lymphoid cells (ILC2s), in shaping the tumor microenvironment and immune responses, we investigated the contribution of ILC2s in bladder tumor development. Using the orthotopic murine MB49 bladder tumor model, we found a strong enrichment of ILC2s in the bladder under steady-state conditions, comparable to that in the lung. However, as tumors grew, we observed an increase in ILC1s but no changes in ILC2s. Targeting ILC2s by blocking IL-4/IL-13 signaling pathways, IL-5, or IL-33 receptor, or using IL-33-deficient or ILC2-deficient mice, did not affect mice survival following bladder tumor implantation. Overall, these results suggest that ILC2s do not contribute significantly to bladder tumor development, yet further investigations are required to confirm these results in bladder cancer patients.

摘要

膀胱癌患者的治疗方法受到副作用和失败的限制,这凸显了需要新的靶点来改善疾病管理。鉴于越来越多的证据强调了先天淋巴细胞亚群,特别是 2 型先天淋巴细胞(ILC2s),在塑造肿瘤微环境和免疫反应方面的关键作用,我们研究了 ILC2s 在膀胱癌发展中的作用。使用原位鼠 MB49 膀胱癌模型,我们发现 ILC2s 在稳定状态下在膀胱中的富集程度与在肺部相当。然而,随着肿瘤的生长,我们观察到 ILC1s 的增加,但 ILC2s 没有变化。通过阻断 IL-4/IL-13 信号通路、IL-5 或 IL-33 受体,或使用 IL-33 缺陷型或 ILC2 缺陷型小鼠靶向 ILC2s,并没有影响膀胱癌植入后小鼠的存活。总的来说,这些结果表明 ILC2s 对膀胱癌的发展没有显著贡献,但需要进一步的研究来确认这些结果在膀胱癌患者中的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7106/10820705/191ce8bdfdc7/fimmu-14-1335326-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7106/10820705/5555e7a453a3/fimmu-14-1335326-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7106/10820705/81f070297b3c/fimmu-14-1335326-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7106/10820705/3af1e09b788a/fimmu-14-1335326-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7106/10820705/191ce8bdfdc7/fimmu-14-1335326-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7106/10820705/5555e7a453a3/fimmu-14-1335326-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7106/10820705/81f070297b3c/fimmu-14-1335326-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7106/10820705/3af1e09b788a/fimmu-14-1335326-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7106/10820705/191ce8bdfdc7/fimmu-14-1335326-g004.jpg

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本文引用的文献

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Innate lymphoid cells and innate-like T cells in cancer - at the crossroads of innate and adaptive immunity.固有淋巴细胞和类先天 T 细胞在癌症中的作用——先天免疫和适应性免疫的交汇点。
Nat Rev Cancer. 2023 Jun;23(6):351-371. doi: 10.1038/s41568-023-00562-w. Epub 2023 Apr 20.
2
ILC2 require cell-intrinsic ST2 signals to promote type 2 immune responses.ILC2 需要细胞内固有 ST2 信号来促进 2 型免疫反应。
Front Immunol. 2023 Mar 31;14:1130933. doi: 10.3389/fimmu.2023.1130933. eCollection 2023.
3
IL-33-ILC2 axis promotes anti-tumor CD8 T cell responses via OX40 signaling.
IL-33-ILC2 轴通过 OX40 信号促进抗肿瘤 CD8 T 细胞反应。
Biochem Biophys Res Commun. 2022 Dec 31;637:9-16. doi: 10.1016/j.bbrc.2022.11.006. Epub 2022 Nov 5.
4
Group 3 innate lymphocytes make a distinct contribution to type 17 immunity in bladder defence.第3组固有淋巴细胞在膀胱防御中对17型免疫作出独特贡献。
iScience. 2022 Jun 22;25(7):104660. doi: 10.1016/j.isci.2022.104660. eCollection 2022 Jul 15.
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Role of ILC2s in Solid Tumors: Facilitate or Inhibit?固有淋巴样细胞 2 (ILC2s)在实体瘤中的作用:促进还是抑制?
Front Immunol. 2022 Jun 3;13:886045. doi: 10.3389/fimmu.2022.886045. eCollection 2022.
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An innate IL-25-ILC2-MDSC axis creates a cancer-permissive microenvironment for mutation-driven intestinal tumorigenesis.先天 IL-25-ILC2-MDSC 轴为驱动突变的肠道肿瘤发生创造了有利于癌症的微环境。
Sci Immunol. 2022 Jun 3;7(72):eabn0175. doi: 10.1126/sciimmunol.abn0175.
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Innate lymphoid cells and cancer.固有淋巴细胞与癌症。
Nat Immunol. 2022 Mar;23(3):371-379. doi: 10.1038/s41590-022-01127-z. Epub 2022 Feb 28.
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