Spatial Profiling Identifies Regionally Distinct Microenvironments and Targetable Immunosuppressive Mechanisms in Pediatric Osteosarcoma Pulmonary Metastases.

Jason Eigenbrood,Nathan Wong，Rosandra N Kaplan,Troy A McEachron

Cancer research（2025）

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Abstract

Osteosarcoma is the most common malignant bone tumor in young patients and remains a significant clinical challenge, particularly at the metastatic stage. Studies detailing the immunosuppressive mechanisms within the metastatic osteosarcoma microenvironment are needed to elucidate the cellular communities in the metastatic microenvironment that support metastatic growth and to identify therapeutic approaches to target the cross-talk between cancer cells and their microenvironment. In this study, we performed spatial transcriptional profiling on a cohort of osteosarcoma pulmonary metastases from pediatric patients. The data revealed a conserved spatial gene expression pattern resembling a foreign body granuloma, characterized by peripheral inflammatory signaling, fibrocollagenous encapsulation, lymphocyte exclusion, and peritumoral macrophage accumulation. The intratumoral microenvironment of these lesions, however, lacked inflammatory signaling. Exploration of spatially distinct drug-gene interactions identified the CXCR4 signaling axis, which displayed spatial heterogeneity and complexity, as a potential therapeutic target that bridges both the intra- and extratumoral microenvironments. Collectively, this study reveals that metastatic osteosarcoma comprises multiple regionally distinct immunosuppressive microenvironments. SIGNIFICANCE:Exploration of spatially resolved microenvironments in metastatic osteosarcoma tissues reveals how the tissue architecture promotes immunosuppression and identifies actionable processes to enhance immunotherapy efficacy.

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【要点】：该论文通过空间转录组分析揭示了儿童骨肉瘤肺转移灶中的区域特异性微环境和可靶向的免疫抑制机制，发现了CXCR4作为潜在的免疫调节治疗靶点。

【方法】：研究采用空间转录组技术对儿童骨肉瘤肺转移灶进行基因表达分析。

【实验】：实验在儿童骨肉瘤肺转移灶样本上进行，通过空间转录组技术揭示了病变区域的免疫抑制微环境特征，并确定了CXCR4作为治疗靶点的潜力。数据集名称未提及。

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