Spatial transcriptomics reveal topological immune landscapes of Asian head and neck angiosarcoma

Abstract

Abstract Angiosarcomas are rare malignant tumors of the endothelium, arising commonly from the head and neck region (AS-HN) and recently associated with ultraviolet (UV) exposure and human herpesvirus-7 infection. We examined 81 cases of angiosarcomas, including 47 cases of AS-HN, integrating information from whole genome sequencing, gene expression profiling and spatial transcriptomics (10X Visium). In the AS-HN cohort, we observed recurrent somatic mutations in CSMD3 (18%), LRP1B (18%), MUC16 (18%), POT1 (16%) and TP53 (16%). UV-positive AS-HN harbored significantly higher tumor mutation burden than UV-negative cases (p = 0.0294). NanoString profiling identified three clusters with distinct tumor inflammation signature scores (p < 0.001). Spatial transcriptomics revealed topological profiles of the tumor microenvironment, identifying dominant but tumor-excluded inflammatory signals in immune-hot cases and immune foci even in otherwise immune-cold cases. In conclusion, spatial transcriptomics reveal the tumor immune landscape of angiosarcoma, and in combination with multi-omic information, may improve implementation of treatment strategies.