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在单细胞水平上对肿瘤微环境进行表征揭示了骨肉瘤中一种新的免疫逃逸机制。

Characterizing the tumor microenvironment at the single-cell level reveals a novel immune evasion mechanism in osteosarcoma.

作者信息

Liu Weijian, Hu Hongzhi, Shao Zengwu, Lv Xiao, Zhang Zhicai, Deng Xiangtian, Song Qingcheng, Han Yong, Guo Tao, Xiong Liming, Wang Baichuan, Zhang Yingze

机构信息

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, China.

出版信息

Bone Res. 2023 Jan 3;11(1):4. doi: 10.1038/s41413-022-00237-6.


DOI:10.1038/s41413-022-00237-6
PMID:36596773
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9810605/
Abstract

The immune microenvironment extensively participates in tumorigenesis as well as progression in osteosarcoma (OS). However, the landscape and dynamics of immune cells in OS are poorly characterized. By analyzing single-cell RNA sequencing (scRNA-seq) data, which characterize the transcription state at single-cell resolution, we produced an atlas of the immune microenvironment in OS. The results suggested that a cluster of regulatory dendritic cells (DCs) might shape the immunosuppressive microenvironment in OS by recruiting regulatory T cells. We also found that major histocompatibility complex class I (MHC-I) molecules were downregulated in cancer cells. The findings indicated a reduction in tumor immunogenicity in OS, which can be a potential mechanism of tumor immune escape. Of note, CD24 was identified as a novel "don't eat me" signal that contributed to the immune evasion of OS cells. Altogether, our findings provide insights into the immune landscape of OS, suggesting that myeloid-targeted immunotherapy could be a promising approach to treat OS.

摘要

免疫微环境广泛参与骨肉瘤(OS)的肿瘤发生及进展。然而,OS中免疫细胞的格局和动态变化目前仍知之甚少。通过分析单细胞RNA测序(scRNA-seq)数据(该数据可在单细胞分辨率下表征转录状态),我们构建了OS免疫微环境图谱。结果表明,一群调节性树突状细胞(DCs)可能通过招募调节性T细胞来塑造OS中的免疫抑制微环境。我们还发现,癌细胞中主要组织相容性复合体I类(MHC-I)分子表达下调。这些发现表明OS中肿瘤免疫原性降低,这可能是肿瘤免疫逃逸的潜在机制。值得注意的是,CD24被鉴定为一种新的“别吃我”信号,它有助于OS细胞的免疫逃逸。总之,我们的研究结果为OS的免疫格局提供了见解,表明靶向髓系细胞的免疫疗法可能是治疗OS的一种有前景的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94f0/9810605/3a8db1c202b1/41413_2022_237_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94f0/9810605/3c677bc2ae65/41413_2022_237_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94f0/9810605/6f3f8c72b39e/41413_2022_237_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94f0/9810605/78d7a081fdfc/41413_2022_237_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94f0/9810605/f5f3aacbc123/41413_2022_237_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94f0/9810605/8e276d0c3646/41413_2022_237_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94f0/9810605/f5da9250ba09/41413_2022_237_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94f0/9810605/3a8db1c202b1/41413_2022_237_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94f0/9810605/3c677bc2ae65/41413_2022_237_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94f0/9810605/6f3f8c72b39e/41413_2022_237_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94f0/9810605/78d7a081fdfc/41413_2022_237_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94f0/9810605/f5f3aacbc123/41413_2022_237_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94f0/9810605/8e276d0c3646/41413_2022_237_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94f0/9810605/f5da9250ba09/41413_2022_237_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94f0/9810605/3a8db1c202b1/41413_2022_237_Fig7_HTML.jpg

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[1]
Characterizing the tumor microenvironment at the single-cell level reveals a novel immune evasion mechanism in osteosarcoma.

Bone Res. 2023-1-3

[2]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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引用本文的文献

[1]
Molecular and Glycosylation Pathways in Osteosarcoma: Tumor Microenvironment and Emerging Strategies Toward Personalized Oncology.

Curr Issues Mol Biol. 2025-8-7

[2]
Two-sample Mendelian randomization analysis of the causal association between circulating inflammatory proteins and osteosarcoma.

Discov Oncol. 2025-7-31

[3]
Immunosuppressive Tumor Microenvironment of Osteosarcoma.

Cancers (Basel). 2025-6-24

[4]
Near-infrared light-induced photothermal and immunotherapy system for lung cancer bone metastasis treatment with simultaneous bone repair.

Bioact Mater. 2025-6-10

[5]
From cells to clinic: Single-cell transcriptomics shaping the future of orthopedics.

J Orthop Translat. 2025-5-28

[6]
Single‑cell transcriptomic analysis revealed the tumor‑associated microenvironment of papillary thyroid carcinoma with metastasis.

Oncol Lett. 2025-1-7

[7]
Harnessing multi‑omics to revolutionize understanding and management of osteosarcoma: A pathway to precision medicine (Review).

Int J Mol Med. 2025-6

[8]
Microenvironment matters: insights from the FOSTER consortium on microenvironment-driven approaches to osteosarcoma therapy.

Cancer Metastasis Rev. 2025-4-10

[9]
The role of B2M in cancer immunotherapy resistance: function, resistance mechanism, and reversal strategies.

Front Immunol. 2025-3-21

[10]
The neutrophil extracellular trap-related gene FPR1 (formyl peptide receptor 1) as a potential prognostic and therapeutic target in osteosarcoma.

BMC Musculoskelet Disord. 2025-3-31

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