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CD301b+单核细胞衍生的树突状细胞介导对放疗的抗性。

CD301b+ monocyte-derived dendritic cells mediate resistance to radiotherapy.

作者信息

Tadepalli Sirimuvva, Clements Derek R, Raquer-McKay Hayley M, Lüdtke Anja, Saravanan Sanjana, Seong David, Vitek Lorraine, Richards Christopher M, Carette Jan E, Mack Matthias, Gottfried-Blackmore Andres, Graves Edward E, Idoyaga Juliana

机构信息

Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.

Immunology Program, Stanford University School of Medicine , Stanford, CA, USA.

出版信息

J Exp Med. 2025 Jun 2;222(6). doi: 10.1084/jem.20231717. Epub 2025 Mar 27.

DOI:10.1084/jem.20231717
PMID:40146036
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11949126/
Abstract

Monocytes infiltrating tumors acquire various states that distinctly impact cancer treatment. Here, we show that resistance of tumors to radiotherapy (RT) is controlled by the accumulation of monocyte-derived dendritic cells (moDCs). These moDCs are characterized by the expression of CD301b and have a superior capacity to generate regulatory T cells (Tregs). Accordingly, moDC depletion limits Treg generation and improves the therapeutic outcome of RT. Mechanistically, we demonstrate that granulocyte-macrophage colony-stimulating factor (GM-CSF) derived from radioresistant tumor cells following RT is necessary for the accumulation of moDCs. Our results unravel the immunosuppressive function of moDCs and identify GM-CSF as an immunotherapeutic target during RT.

摘要

浸润肿瘤的单核细胞会呈现出多种状态，这些状态对癌症治疗有着截然不同的影响。在此，我们表明肿瘤对放疗（RT）的抗性是由单核细胞衍生的树突状细胞（moDC）的积累所控制的。这些moDC以CD301b的表达为特征，并且具有产生调节性T细胞（Treg）的卓越能力。因此，去除moDC会限制Treg的产生，并改善放疗的治疗效果。从机制上来说，我们证明放疗后源自放射抗性肿瘤细胞的粒细胞-巨噬细胞集落刺激因子（GM-CSF）对于moDC的积累是必需的。我们的研究结果揭示了moDC的免疫抑制功能，并确定GM-CSF是放疗期间的一个免疫治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54e5/11949126/dc60fd403187/jem_20231717_fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54e5/11949126/f4befb8044b8/jem_20231717_ga.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54e5/11949126/2cd9b7e9857a/jem_20231717_fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54e5/11949126/519489f08a9b/jem_20231717_figs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54e5/11949126/83d1890c6364/jem_20231717_fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54e5/11949126/68ffb3ff63e4/jem_20231717_figs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54e5/11949126/0bc6c7c9aac6/jem_20231717_figs3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54e5/11949126/6ceb6b40037f/jem_20231717_fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54e5/11949126/db860d02d373/jem_20231717_figs4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54e5/11949126/ccbb1d710c65/jem_20231717_fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54e5/11949126/9daade41d265/jem_20231717_fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54e5/11949126/355d306cdafc/jem_20231717_figs5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54e5/11949126/dc60fd403187/jem_20231717_fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54e5/11949126/f4befb8044b8/jem_20231717_ga.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54e5/11949126/2cd9b7e9857a/jem_20231717_fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54e5/11949126/519489f08a9b/jem_20231717_figs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54e5/11949126/83d1890c6364/jem_20231717_fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54e5/11949126/68ffb3ff63e4/jem_20231717_figs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54e5/11949126/0bc6c7c9aac6/jem_20231717_figs3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54e5/11949126/6ceb6b40037f/jem_20231717_fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54e5/11949126/db860d02d373/jem_20231717_figs4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54e5/11949126/ccbb1d710c65/jem_20231717_fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54e5/11949126/9daade41d265/jem_20231717_fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54e5/11949126/355d306cdafc/jem_20231717_figs5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54e5/11949126/dc60fd403187/jem_20231717_fig6.jpg

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本文引用的文献

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Sintilimab in combination with stereotactic body radiotherapy and granulocyte-macrophage colony-stimulating factor in metastatic non-small cell lung cancer: The multicenter SWORD phase 2 trial.西妥昔单抗联合立体定向放疗和粒细胞-巨噬细胞集落刺激因子治疗转移性非小细胞肺癌：多中心 SWORD 期 2 试验。
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Timing and location dictate monocyte fate and their transition to tumor-associated macrophages.
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