Bagaria Sanjay P, Gatalica Zoran, Maney Todd, Serie Daniel, Parasramka Mansi, Attia Steven, Krishna Murli, Joseph Richard W
Department of Surgery, Division of General Surgery, Mayo Clinic, Jacksonville, FL, United States.
Caris Life Sciences, Phoenix, AZ, United States.
Front Oncol. 2018 Mar 22;8:71. doi: 10.3389/fonc.2018.00071. eCollection 2018.
Angiosarcoma is a vascular malignancy associated with a poor prognosis and chemotherapy resistance. The tumor immune microenvironment of angiosarcoma has not been characterized. We investigated the expression of programmed death-ligand 1 (PD-L1) and programmed death 1 (PD-1) in angiosarcoma and correlated these findings with vascular endothelial growth factor (VEGF)-related gene expression and survival. Using archived formalin-fixed paraffin-embedded tissues of primary and metastatic angiosarcoma specimens, we characterized the immunohistochemical (IHC) expression of PD-L1 and PD-1. In addition, we extracted RNA from each tumor and quantified the expression of VEGF-related genes, and then tested if these genes were associated with PD-L1 and PD-1 expression and clinical outcomes. Retrospective review identified 27 angiosarcoma specimens collected between 1994 and 2012. IHC expression of tumor PD-L1, tumor-infiltrating immune cell PD-L1, and tumor-infiltrating immune cell PD-1 expression was identified in 5 (19%), 9 (33%), and 1 (4%) specimens, respectively. Expression of PD-L1 and PD-1 was not associated with VEGF-related gene expression or survival. PD-L1 tumor and tumor-infiltrating immune cells expression was identified in a large proportion of patients. Though neither was associated with VEGF-related gene expression or prognosis, targeting PD-1/PD-L1 may be of benefit for a significant proportion of angiosarcomas that do not respond to surgery, chemotherapy, or radiation.
血管肉瘤是一种预后不良且具有化疗耐药性的血管恶性肿瘤。血管肉瘤的肿瘤免疫微环境尚未得到明确描述。我们研究了程序性死亡配体1（PD-L1）和程序性死亡1（PD-1）在血管肉瘤中的表达，并将这些发现与血管内皮生长因子（VEGF）相关基因表达及生存率相关联。我们使用原发性和转移性血管肉瘤标本的存档福尔马林固定石蜡包埋组织，对PD-L1和PD-1进行免疫组织化学（IHC）表达特征分析。此外，我们从每个肿瘤中提取RNA，对VEGF相关基因的表达进行定量，然后测试这些基因是否与PD-L1和PD-1表达及临床结果相关。回顾性研究确定了1994年至2012年间收集的27个血管肉瘤标本。分别在5个（19%）、9个（33%）和1个（4%）标本中检测到肿瘤PD-L1、肿瘤浸润免疫细胞PD-L1和肿瘤浸润免疫细胞PD-1的IHC表达。PD-L1和PD-1的表达与VEGF相关基因表达或生存率无关。在很大一部分患者中检测到了PD-L1在肿瘤及肿瘤浸润免疫细胞中的表达。尽管二者均与VEGF相关基因表达或预后无关，但对于很大一部分对手术、化疗或放疗无反应的血管肉瘤患者，靶向PD-1/PD-L1可能有益。
