Unraveling the tumor immune microenvironment of angiosarcomas

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Yvonne Versleijen-Jonkers, PhD,  Radboud University Nijmegen Medical Center
Recipient of the: $50,000 Catherine Malatesta Memorial Research Award

Is immune checkpoint inhibition the solution for angiosarcoma patients? Genetic and immune profiles of angiosarcoma subtypes will lead to novel insights for the design of individualized immune checkpoint-based therapy for AS patients.

Angiosarcomas are rare and aggressive tumors that arise from the vascular endothelium. Despite all therapeutic efforts, the prognosis for angiosarcoma patients is very poor with a 5-year survival of only 30-40%, urging the need for novel therapeutic approaches for these patients. Angiosarcomas can present anywhere in the body and can either develop spontaneously (primary angiosarcomas) or due to previous radiotherapy, chronic lymphedema, or exposure to UV radiation (secondary angiosarcomas). The clinical behavior and prognosis of the angiosarcoma subtypes differ. This heterogeneity urges the characterization of clinically relevant subtypes and the exploration of therapeutic strategies on a subtype specific level.
Immune checkpoint inhibitors (ICI) are a major breakthrough in the treatment of cancer. In some recent angiosarcoma case reports and small case series promising partial or complete responses on ICI were seen, especially in the UV induced subtype. There is a lack of preclinical data on the immune profiles of angiosarcoma subtypes and tumor pathways that might enhance the responsiveness to ICI. In theory, several synergistic combinations can be expected in especially secondary angiosarcomas.
We aim to improve the immunological treatment of angiosarcomas by mapping the immunological microenvironment of the different angiosarcoma subtypes and define strategies that enhance the responsiveness to ICI. Ultimately, after this project we have unraveled the tumor immune microenvironment for the different angiosarcoma subtypes, found additional synergistic targets and translated this in the most optimal treatment strategies to be further tested in each subtype.