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Immunological and Genomic Analysis Reveals Clinically Relevant Distinctions between Angiosarcoma Subgroups.

Stefan G van Ravensteijn1, Yvonne M H Versleijen-Jonkers1, Melissa H S Hillebrandt-Roeffen1

  • 1Department of Medical Oncology, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands.

Cancers
|December 11, 2022
PubMed
Summary

Primary and secondary angiosarcomas show distinct immune cell infiltration and genomic profiles. Secondary angiosarcomas exhibit higher T-cell infiltration and DNA damage response mutations, suggesting potential for immunotherapy.

Keywords:
angiosarcomabiomarkergeneticsimmunotherapysarcomatumor microenvironment

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Area of Science:

  • Oncology
  • Immunology
  • Genomics

Background:

  • Angiosarcomas (AS) are rare, aggressive vascular cancers.
  • AS are classified as primary (pAS) or secondary (sAS).
  • Distinct immunological and genomic profiles may influence treatment, including immunotherapy.

Purpose of the Study:

  • To investigate differences in immune infiltration and genomic profiles between pAS and sAS.
  • To explore the potential impact on treatment strategies and immunotherapy efficacy.

Main Methods:

  • Multiplex immunohistochemistry analyzed tumor-infiltrating lymphocytes in 79 pAS and 178 sAS.
  • Comprehensive genomic profiling was performed on 25 pAS and 25 sAS.
  • Analysis included T-cells (CD3+, CD8+, CD4+, FoxP3+) and B-cells (CD20+).

Main Results:

  • Secondary AS showed significantly higher densities of CD3+, CD8+, CD4+, and FoxP3+ T-cells compared to primary AS.
  • Genomic profiling revealed frequent amplifications (84% vs. 15%) and DNA damage response (DDR) pathway mutations in sAS.
  • MYC amplifications were also predominantly observed in sAS.

Conclusions:

  • A clear clinical distinction exists between pAS and sAS in immune infiltration and genomic landscapes.
  • The T-cell-rich microenvironment and frequent DDR mutations in sAS support further investigation into immunotherapy clinical trials.