Multiomic analysis and immunoprofiling reveal distinct subtypes of human angiosarcoma

Angiosarcomas are rare, clinically aggressive tumors with limited treatment options and a dismal prognosis. We analyzed angiosarcomas from 68 patients, integrating information from multiomic sequencing, NanoString immuno-oncology profiling, and multiplex immunohistochemistry and immunofluorescence for tumor-infiltrating immune cells. Through whole-genome sequencing (n = 18), 50% of the cutaneous head and neck angiosarcomas exhibited higher tumor mutation burden (TMB) and UV mutational signatures; others were mutationally quiet and non–UV driven. NanoString profiling revealed 3 distinct patient clusters represented by lack (clusters 1 and 2) or enrichment (cluster 3) of immune-related signaling and immune cells. Neutrophils (CD15+), macrophages (CD68+), cytotoxic T cells (CD8+), Tregs (FOXP3+), and PD-L1+ cells were enriched in cluster 3 relative to clusters 2 and 1. Likewise, tumor inflammation signature (TIS) scores were highest in cluster 3 (7.54 vs. 6.71 vs. 5.75, respectively; P

Source: Journal of Clinical Investigation - October 6, 2020 Category: Biomedical Science Authors: Jason Yongsheng Chan, Jing Quan Lim, Joe Yeong, Vinod Ravi, Peiyong Guan, Arnoud Boot, Timothy Kwang Yong Tay, Sathiyamoorthy Selvarajan, Nur Diyana Md Nasir, Jie Hua Loh, Choon Kiat Ong, Dachuan Huang, Jing Tan, Zhimei Li, Cedric Chuan-Young Ng, Thuan To Source Type: research