Association Between Programmed Death-Ligand 1 Expression and the Vascular Endothelial Growth Factor Pathway in Angiosarcoma
Association Between Programmed Death-Ligand 1 Expression and the Vascular Endothelial Growth Factor Pathway in Angiosarcoma
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DOI：
10.3389/fonc.2018.00071
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发表时间：
2018-03-22
影响因子：
4.7
通讯作者：
Joseph, Richard W.
中科院分区：
文献类型：
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作者：
Bagaria, Sanjay P.;Gatalica, Zoran;Joseph, Richard W.
血管肉瘤是一种与预后不良和化疗耐药相关的血管恶性肿瘤。血管肉瘤的肿瘤免疫微环境尚不清楚。我们检测了程序性死亡配体1(PD-L1)和程序性死亡1(PD-1)在血管肉瘤中的表达，并将其与血管内皮生长因子(VEGF)相关基因表达和生存期的关系进行了研究。采用福尔马林固定石蜡包埋的原发和转移性血管肉瘤组织标本，研究PD-L1和PD-1的免疫组织化学(IHC)表达。此外，我们从每个肿瘤中提取RNA并定量检测血管内皮生长因子相关基因的表达，然后检验这些基因是否与PD-L1和PD-1的表达以及临床预后相关。回顾发现了1994至2012年间收集的27例血管肉瘤标本。肿瘤PD-L1表达5例(19%)，肿瘤浸润性免疫细胞PD-L1表达9例(33%)，肿瘤浸润性免疫细胞PD-1表达1例(4%)。PD-L1和PD-1的表达与血管内皮生长因子相关基因的表达和生存期无关。PD-L1肿瘤和肿瘤浸润性免疫细胞在很大比例的患者中都有表达。虽然两者都与血管内皮生长因子相关基因的表达或预后无关，但靶向PD-1/PD-L1对手术、化疗或放疗无效的相当大比例的血管肉瘤可能是有益的。
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.