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Multiomic analysis and immunoprofiling reveal distinct subtypes of human angiosarcoma
Jason Yongsheng Chan1,2,3, Jing Quan Lim4, Joe Yeong5,6
1Division of Medical Oncology, National Cancer Centre Singapore, Singapore.
The Journal of Clinical Investigation
|October 5, 2020
Summary
This study analyzes angiosarcomas, revealing distinct molecular subtypes. Some tumors respond to immunotherapy, while others may benefit from targeted therapies based on their unique genetic profiles.
Area of Science:
- Oncology
- Genomics
- Immunology
Background:
- Angiosarcomas are rare, aggressive cancers with poor outcomes.
- Limited effective treatment options exist for angiosarcoma patients.
Purpose of the Study:
- To molecularly and immunologically characterize angiosarcomas.
- To identify potential therapeutic strategies for distinct angiosarcoma subtypes.
Main Methods:
- Multiomic sequencing (whole-genome sequencing) was performed on 68 angiosarcoma patients.
- NanoString immuno-oncology profiling and multiplex immunohistochemistry/immunofluorescence were used.
- Tumor-infiltrating immune cells and molecular pathways were analyzed.
Main Results:
- Cutaneous head and neck angiosarcomas showed high tumor mutation burden (TMB) and UV signatures in 50% of cases.
- Three patient clusters emerged: two with low immune infiltration and one with high immune cell enrichment (neutrophils, macrophages, T cells, Tregs, PD-L1+ cells).
- Cluster 3, with high TMB and tumor inflammation signature (TIS) scores, is a candidate for checkpoint immunotherapy. Cluster 2, enriched for secondary angiosarcomas, showed upregulated epigenetic and oncogenic pathways.
Conclusions:
- Molecular and immunological profiling reveals distinct angiosarcoma subtypes.
- Head and neck angiosarcomas with high TMB and TIS scores may respond to immunotherapy.
- Secondary angiosarcomas with specific pathway activations could be targeted with precision therapies.
