文章：

骨肉瘤的免疫抑制性肿瘤微环境

Immunosuppressive Tumor Microenvironment of Osteosarcoma

原文发布日期：24 June 2025

DOI: 10.3390/cancers17132117

类型: Article

开放获取: 是

英文摘要：

Background/Objectives:Osteosarcoma is the most common malignant bone tumor in children, characterized by a high degree of genomic instability, resulting in copy number alterations and genomic rearrangements without disease-defining recurrent mutations. Clinical trials based on molecular characterization have failed to find new effective therapies or improve outcomes over the last 40 years.Methods:To better understand the immune microenvironment of osteosarcoma, we performed single-cell RNA sequencing on six tumor biopsy samples, combined with a previously published cohort of six samples. Additional osteosarcoma samples were profiled using spatial transcriptomics for the validation of discovered subtypes and to add spatial context.Results:Analysis revealed immunosuppressive cells, including myeloid-derived suppressor cells (MDSCs), regulatory and exhausted T cells, and LAMP3+ dendritic cells.Conclusions:Using cell–cell communication modeling, we identified robust interactions between MDSCs and other cells, leading to NF-κB upregulation and an immunosuppressive microenvironment, as well as interactions involving regulatory T cells and osteosarcoma cells that promoted tumor progression and a proangiogenic niche.

摘要翻译： 

背景/目的：骨肉瘤是儿童中最常见的恶性骨肿瘤，其特点是基因组高度不稳定，导致拷贝数改变和基因组重排，但缺乏疾病定义性的复发性突变。过去40年间，基于分子特征开展的临床试验未能发现新的有效疗法或改善患者预后。 方法：为深入理解骨肉瘤的免疫微环境，我们对六例肿瘤活检样本进行了单细胞RNA测序，并结合先前已发表的六例样本队列数据。同时采用空间转录组学技术对更多骨肉瘤样本进行分析，以验证发现的亚型并补充空间背景信息。 结果：分析揭示了多种免疫抑制细胞的存在，包括髓源性抑制细胞（MDSCs）、调节性T细胞与耗竭T细胞，以及LAMP3+树突状细胞。 结论：通过细胞间通讯模型分析，我们发现了MDSCs与其他细胞间存在显著的相互作用，导致NF-κB信号通路上调并形成免疫抑制微环境；同时揭示了调节性T细胞与骨肉瘤细胞间的相互作用促进了肿瘤进展并形成促血管生成微环境。

原文链接：

Immunosuppressive Tumor Microenvironment of Osteosarcoma