Association Between Programmed Death-Ligand 1 Expression and the Vascular Endothelial Growth Factor Pathway in Angiosarcoma

• Main Authors: Sanjay P. Bagaria, Zoran Gatalica, Todd Maney, Daniel Serie, Mansi Parasramka, Steven Attia, Murli Krishna, Richard W. Joseph
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2018-03-01
• Series: Frontiers in Oncology
• Subjects: angiosarcoma; programmed death-ligand 1; immune microenvironment; checkpoint pathway; vascular endothelial growth factor
• Online Access: http://journal.frontiersin.org/article/10.3389/fonc.2018.00071/full

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.