Department of Translational Genomics, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
NanoString Technologies, Inc., Seattle, WA, USA.
Oncoimmunology. 2019 Jun 27;8(9):e1629779. doi: 10.1080/2162402X.2019.1629779. eCollection 2019.
Osteosarcoma (OS) is the most common bone tumor in pediatric and adolescent/young adult patients yet little is known about the microenvironment that supports this aggressive disease. We have used targeted gene expression profiling and immunohistochemistry to characterize the microenvironment of metastatic and non-metastatic OS specimens from pediatric patients exhibiting poor histologic response to chemotherapy. Our results indicate that metastatic specimens exhibit lymphocyte exclusion as T cells are confined to the periphery of the pulmonary lesions. Furthermore, our data provides evidence of vascular dysfunction in metastatic OS indicated by increased expression of , an increased gene expression ratio, and decreased expression of , the gene encoding the adhesion molecule E-selectin. Moreover, correlation analyses show an inverse relationship between lymphocyte abundance and markers of vascular dysfunction exclusively in the metastatic specimens. Together, our data shows that the non-metastatic OS specimens demonstrate increased expression of various immunotherapeutic targets in comparison metastatic specimens and identifies vascular dysfunction and lymphocyte exclusion as important processes for therapeutic intervention in metastatic disease.
骨肉瘤（OS）是儿童和青少年/年轻成人患者中最常见的骨肿瘤，但对于支持这种侵袭性疾病的微环境知之甚少。我们使用靶向基因表达谱分析和免疫组织化学技术，对来自表现出对化疗不良组织学反应的儿科患者的转移性和非转移性 OS 标本的微环境进行了特征描述。我们的结果表明，转移性标本表现出淋巴细胞排斥现象，因为 T 细胞局限于肺病变的外围。此外，我们的数据提供了转移性 OS 血管功能障碍的证据，表现为 、基因表达比值增加和编码粘附分子 E-选择素的 基因表达减少。此外，相关分析显示，仅在转移性标本中，淋巴细胞丰度与血管功能障碍标志物之间存在反比关系。总之，我们的数据表明，与转移性标本相比，非转移性 OS 标本表现出各种免疫治疗靶标的表达增加，并确定血管功能障碍和淋巴细胞排斥是转移性疾病治疗干预的重要过程。
