Department of Orthopaedics, West Virginia University School of Medicine, Morgantown, WV, 26506, USA.
Cancer Institute, West Virginia University School of Medicine, Morgantown, WV, 26506, USA.
Bone Res. 2024 Sep 27;12(1):55. doi: 10.1038/s41413-024-00359-z.
Patients diagnosed with advanced osteosarcoma, often in the form of lung metastases, have abysmal five-year overall survival rates. The complexity of the osteosarcoma immune tumor microenvironment has been implicated in clinical trial failures of various immunotherapies. The purpose of this exploratory study was to spatially characterize the immune tumor microenvironment of metastatic osteosarcoma lung specimens. Knowledge of the coordinating cellular networks within these tissues could then lead to improved outcomes when utilizing immunotherapy for treatment of this disease. Importantly, various cell types, interactions, and cellular neighborhoods were associated with five-year survival status. Of note, increases in cellular interactions between T lymphocytes, positive for programmed cell death protein 1, and myeloid-derived suppressor cells were observed in the 5-year deceased cohort. Additionally, cellular neighborhood analysis identified an Immune-Cold Parenchyma cellular neighborhood, also associated with worse 5-year survival. Finally, the Osteosarcoma Spatial Score, which approximates effector immune activity in the immune tumor microenvironment through the spatial proximity of immune and tumor cells, was increased within 5-year survivors, suggesting improved effector signaling in this patient cohort. Ultimately, these data represent a robust spatial multiplexed immunofluorescence analysis of the metastatic osteosarcoma immune tumor microenvironment. Various communication networks, and their association with survival, were described. In the future, identification of these networks may suggest the use of specific, combinatory immunotherapeutic strategies for improved anti-tumor immune responses and outcomes in osteosarcoma.
患有晚期骨肉瘤的患者，通常表现为肺转移，其五年总体生存率极低。骨肉瘤免疫肿瘤微环境的复杂性与各种免疫疗法临床试验失败有关。本探索性研究的目的是对转移性骨肉瘤肺标本的免疫肿瘤微环境进行空间特征分析。了解这些组织中协调的细胞网络，当利用免疫疗法治疗这种疾病时，可能会改善预后。重要的是，各种细胞类型、相互作用和细胞邻域与五年生存状态相关。值得注意的是，在五年内死亡的队列中观察到程序性细胞死亡蛋白 1 阳性 T 淋巴细胞与髓样来源抑制细胞之间的细胞相互作用增加。此外，细胞邻域分析确定了免疫冷实质细胞邻域，也与五年生存率较差相关。最后，骨肉瘤空间评分通过免疫和肿瘤细胞的空间接近度来估计免疫肿瘤微环境中的效应免疫活性，在五年生存者中增加，表明该患者群体中的效应信号增强。最终，这些数据代表了对转移性骨肉瘤免疫肿瘤微环境的强大空间多重免疫荧光分析。描述了各种通讯网络及其与生存的关系。将来，这些网络的鉴定可能表明使用特定的、组合性免疫治疗策略，以改善骨肉瘤的抗肿瘤免疫反应和结果。
