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

在单细胞水平上表征肿瘤微环境揭示了骨肉瘤的一种新的免疫逃避机制

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

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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