Abstract
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.
Highlights
Angiosarcoma is an aggressive vascular soft tissue sarcoma thought to arise from mesenchymal cells [1]
Formalin-fixed paraffin-embedded (FFPE) blocks were retrieved and 5 μm slides were reviewed by a board-certified surgery, and the Kaplan–Meier method was used to visualize how outcomes differed between programmed death-ligand 1 (PD-L1) positive and negative patients
Vascular endothelial growth factor (VEGF)-related gene expression and prognosis did not change. Another set of limitations with this study center on biological issues. These include [1] the study included primary, recurrent, and metastatic angiosarcoma specimens, and multiple studies have shown stability in expression between primary and metastatic sites [25], it is not known if PD-L1 expression evolves for angiosarcoma; [2] the intratumoral heterogeneity of PD-L1 expression is not known, and, the spatial location of the sample tested may alter our findings; and [3] anti-programmed death 1 (PD-1) therapy was recently approved for any tumor with mismatch
Summary
Angiosarcoma is an aggressive vascular soft tissue sarcoma thought to arise from mesenchymal cells [1]. The presence of tumor-infiltrating lymphocytes (TILs) has been reported as a manifestation of this phenomenon and is associated with the prognosis of numerous cancers [5], and in particular, CD8+ TILs has been shown to have a positive effect on overall survival for patients with cutaneous angiosarcoma [6]. Another key component of the tumor microenvironment and immune evasion is the expression of the immune checkpoint pathway programmed death 1 (PD-1) and programmed death-ligand 1.
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