Immunological and Genomic Analysis Reveals Clinically Relevant Distinctions between Angiosarcoma Subgroups.
| Title: | Immunological and Genomic Analysis Reveals Clinically Relevant Distinctions between Angiosarcoma Subgroups. |
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| Authors: | van Ravensteijn, Stefan G., Versleijen-Jonkers, Yvonne M. H., Hillebrandt-Roeffen, Melissa H. S., Weidema, Marije E., Nederkoorn, Maikel J. L., Bol, Kalijn F., Gorris, Mark A. J., Verrijp, Kiek, Kroeze, Leonie I., de Bitter, Tessa J. J., de Voer, Richarda M., Flucke, Uta E., Desar, Ingrid M. E. |
| Source: | Cancers; Dec2022, Vol. 14 Issue 23, p5938, 14p |
| Subject Terms: | BIOMARKERS, IMMUNOCHEMISTRY, GENETICS, GENETIC mutation, B cell lymphoma, REGULATORY T cells, GENOMICS, CELL lines, SARCOMA, IMMUNOTHERAPY, RARE diseases, T-cell lymphoma |
| Abstract: | Simple Summary: Angiosarcomas (AS) are rare and aggressive soft tissue sarcomas that can be subdivided in de novo primary AS and secondary AS. They have a very poor prognosis and only limited treatment options are available. Immunotherapy is not registered as treatment for AS. Characterization of the immunological landscape of AS and combining this with genetic data enables possible identification of subgroups that are likely to benefit from immunotherapy based treatment strategies. We observed profound clinically relevant differences in a large group of primary and secondary AS. The T-cell infiltrated tumor microenvironment and frequent DNA Damage Response gene mutations, especially in secondary AS, warrant trials with immunotherapy for this subgroup. Angiosarcomas (AS) are extremely rare and aggressive vascular malignancies subdivided in de novo primary AS (pAS) and secondary AS (sAS). We hypothesize that the combination of immunological and genomic profiles significantly differs between primary and secondary AS, with potential impact on treatment strategies and a role for immunotherapy. Tumor-infiltrating lymphocytes were analyzed using multiplex immunohistochemistry from 79 pAS and 178 sAS. Median cell density was significantly higher in sAS for CD3+ T-cells (p < 0.001), CD8+ cytotoxic T-cells (p = 0.033), CD4+ T-helper cells (p < 0.001) and FoxP3+ T-regulatory cells (p < 0.001). CD20+ B-cell density was comparable (p = 0.417). Comprehensive genomic profiling was performed in 25 pAS and 25 sAS. A (likely) pathogenic mutation was detected in 80% of pAS vs. 88% of sAS (p = 0.702). Amplifications were found in 15% of pAS vs. 84% of sAS (p < 0.001). DNA damage response (DDR) pathway mutations (p = 0.021) and MYC amplifications (p < 0.001) were predominantly seen in sAS. In conclusion we observed a clear and clinical relevant distinction in immune infiltration and genomic profiles between pAS and sAS. The T-cell infiltrated tumor microenvironment and frequent DDR gene mutations, especially in sAS, warrant clinical trials with immunotherapy. [ABSTRACT FROM AUTHOR] |
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| Database: | Complementary Index |
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