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Original Article | Open Access

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

Weijian Liu1,2,Hongzhi Hu1,2,Zengwu Shao1,Xiao Lv1Zhicai Zhang1Xiangtian Deng3Qingcheng Song3,4,5Yong Han6Tao Guo7Liming Xiong1 ( )Baichuan Wang1( )Yingze Zhang1,2,3,4( )
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
Orthopaedic Institute of Hebei Province, Shijiazhuang 050051, China
Key Laboratory of Biomechanics of Hebei Province, Shijiazhuang 050051, China
Animal Center of Hebei Ex & In vivo Biotechnology, Shijiazhuang 050051, China
Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

These authors contributed equally: Weijian Liu, Hongzhi Hu, Zengwu Shao

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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.

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Bone Research
Article number: 4
Cite this article:
Liu W, Hu H, Shao Z, et al. Characterizing the tumor microenvironment at the single-cell level reveals a novel immune evasion mechanism in osteosarcoma. Bone Research, 2023, 11: 4. https://doi.org/10.1038/s41413-022-00237-6

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Received: 20 July 2021
Revised: 08 July 2022
Accepted: 04 September 2022
Published: 03 January 2023
© The Author(s) 2023

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