Analysis of PD-1, PD-L1, and T-cell infiltration in angiosarcoma pathogenetic subgroups.

Angiosarcoma (AS) is a rare malignancy with a poor prognosis. It can develop spontaneously or due to previous radiotherapy (RT), ultraviolet (UV) radiation, or lymphoedema (Stewart Treves AS). Novel therapeutic approaches are needed, but progress is hindered because of the heterogeneity and rarity of AS. In order to explore the potential of immune checkpoint inhibition (ICI), we investigated the protein expression of programmed cell death 1 (PD-1), programmed death-ligand 1 (PD-L1), and CD8 + T cells in 165 AS cases in relation to AS subgroups based on clinical classification and in relation to whole-genome methylation profiling based clusters (A1, A2, B1, B2). High PD-L1 and PD-1 expression were predominantly shown in UV-associated, visceral, and soft tissue AS. RT-associated AS showed predominantly high PD-1 expression. CD8 + T cell infiltration was present in the majority of AS samples. Within the UV-associated AS, two different clusters can be distinguished by DNA methylation profiling. Cases in cluster A1 showed higher PD-1 (p = 0.015), PD-L1 (p = 0.015), and CD8 + T cells (p = 0.008) compared to those in cluster B2, suggesting that these UV-AS tumors are more immunogenic than B2 tumors showing a difference even within one subgroup. In soft tissue AS, combined PD-1 and PD-L1 expression showed a trend toward poor survival (p = 0.051), whereas in UV-associated AS, PD-1 expression correlated with better survival (p = 0.035). In conclusion, we show the presence of PD-1, PD-L1, and CD8 + T cells in the majority of AS but reveal differences between and within AS subgroups, providing prognostic information and indicating to be predictive for ICI.

Targeting angiosarcomas of the soft tissues: A challenging effort in a heterogeneous and rare disease.

Angiosarcomas are rare malignant tumors with a heterogeneous clinical presentation and generally poor prognosis. It has been difficult to establish consistent molecular characteristics and driver events in angiosarcoma development. Oncogenic and angiogenesis-related pathways have been investigated pre-clinically and clinically with varying results. A few promising responses to checkpoint inhibitors have been described, but immunological features require further elucidation. With this review we present an overview of the critical biological pathways and processes affected in angiosarcoma, and their potential role in novel, non-cytotoxic, systemic treatments.