骨肉瘤（OS）是一种常见于儿童和青少年的恶性骨肿瘤。OS患者的预后较差，过去几十年来5年生存率很少有显著改善。OS的预后可能与肿瘤相关巨噬细胞（TAMs）的浸润有关。然而，前炎症巨噬细胞（一种TAMs亚型）在OS预后中的作用尚未报道。本研究通过单细胞RNA测序（scRNA-seq）数据确定了七个亚型的TAMs，并将其定义为促血管生成TAMs（Angio-TAMs）、干扰素渲染TAMs（IFN-TAMs）、炎性细胞因子富集TAMs（Inflam-TAMs）、免疫调节TAMs（Reg-TAMs）、与脂质相关TAMs（LA-TAMs）以及类似TAMs的组织驻留巨噬细胞（RTM-TAMs）（包含两个亚细胞类型）。在对每个巨噬细胞亚型进行生存分析后，发现具有Angio-TAMs的患者在生存方面具有最显著的差异。通过差异表达分析获得与Angio-TAMs相关的八个基因，并利用LASSO算法将这些基因构建为预后模型。将临床OS病例样本根据中位风险得分分为高风险组和低风险组。与低风险组相比，高风险组的生存时间更短。还进行了关于两个风险亚组内免疫细胞浸润和免疫检查点分子表达的额外研究。在免疫治疗反应预测方面，发现Angio-TAM相关的基因风险签名与免疫检查点反应呈负相关。此外，相关富集的GO（基因本体）和KEGG（京都基因组和基因组学百科全书）通路主要与肿瘤的惡性进展有关。根据这些发现，Angio-TAM的基因风险签名可能是OS患者潜在的预后生物标志物和新的治疗靶点。请核对并确认ESM文件是否正确识别。 我们已核对并确认该文件可以正确识别。© 2023年。作者（们）独家许可Springer Science+Business Media, LLC，Springer Nature的一部分。

Osteosarcoma (OS) is a malignant bone tumor that most commonly occurs in children and adolescents. OS patients have a poor prognosis, and 5-year survival rates have rarely improved significantly over the past few decades. OS prognosis may be related to the infiltration of tumor-associated macrophages (TAMs). However, the role of proangiogenic macrophages, a subtype of TAMs, in OS prognosis has not been reported. In this study, seven subtypes of TAMs were identified from single-cell RNA sequencing (scRNA-seq) data that we propose defining as proangiogenic TAMs (Angio-TAMs), interferon-primed TAMs (IFN-TAMs), inflammatory cytokine-enriched TAMs (Inflam-TAMs), immune regulatory TAMs (Reg-TAMs), lipid-associated TAMs (LA-TAMs), and resident-tissue macrophages like TAMs (RTM-TAMs) (containing two subcellular types). In the survival analysis of each macrophage subtype, it was found that patients with Angio-TAMs had the most significant difference in survival. Eight genes associated with Angio-TAMs were obtained by differential expression analysis, and these genes were built into a prognostic model using the LASSO algorithm. Clinical OS case samples were categorized into high-risk and low-risk subgroups using median risk scores. In comparison to the low-risk subgroup, the survival time of the high-risk subgroup was much shorter. Additional studies on immune cell infiltration and immune checkpoint molecule expression in the two risk subgroups were carried out. In immunotherapy response prediction, the Angio-TAM-associated gene risk signature was found to be negatively correlated with immune checkpoint responses. In addition, the associated enriched GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways were mainly involved in the malignant progression of tumors. As suggested by these findings, the Angio-TAM gene risk signature may be an underlying prognostic biomarker and novel therapeutic target for OS patients.Kindly check and confirm whether the ESM file is correctly identifiedWe have checked this file and confirmed that it can be correctly identified.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.