Tumor Microenvironment and Its Clinicopathologic and Prognostic Association in Cutaneous and Noncutaneous Angiosarcomas.

Data de publicació: 05/07/2023 Data Ahead of Print: 09/03/2023

Autors de IIS La Fe

• Celia Requena Caballero

  Autor

• Francisco Giner Segura

  Autor

• Jose Luis Cruz Muñoz

  Autor

Autors aliens a IIS La Fe

• Machado, Isidro
• Lopez-Reig, Raquel
• Fernandez-Serra, Antonio
• Traves, Victor
• Lavernia, Javier
• Claramunt, Reyes
• Llombart, Beatriz
• López-Guerrero JA
• Llombart-Bosch, Antonio

Grups d'Investigació

• Cirugía digestiva y Cuidados perioperatorios

  

  Leader

  Matteo Frasson

Abstract

OBJECTIVES: We explored features of the angiosarcoma (AS) tumor microenvironment to discover subtypes that may respond to immunotherapy. METHODS: Thirty-two ASs were included. Tumors were studied by histology, immunohistochemistry (IHC), and gene expression profile using the HTG EdgeSeq Precision Immuno-Oncology Assay. RESULTS: Comparing cutaneous and noncutaneous ASs, the second group showed 155 deregulated genes, and unsupervised hierarchical clustering (UHC) delineated two groups: the first mostly cutaneous AS and the second mainly noncutaneous AS. Cutaneous ASs showed a significantly higher proportion of T cells, natural killer cells, and naive B cells. ASs without MYC amplification revealed a higher immunoscore in comparison with ASs with MYC amplification. PD-L1 was significantly overexpressed in ASs without MYC amplification. UHC showed 135 deregulated genes differentially expressed when comparing ASs from the non-head and neck area with patients who had AS in the head and neck area. ASs from the head and neck area showed high immunoscore. PD1/PD-L1 content was significantly more highly expressed in ASs from the head and neck area. IHC and HTG gene expression profiling revealed a significant correlation between PD1, CD8, and CD20 protein expression but not PD-L1. CONCLUSIONS: Our HTG analyses confirmed a high degree of tumor and microenvironment heterogeneity. Cutaneous ASs, ASs without MYC amplification, and ASs located in the head and neck area seem to be the most immunogenic subtypes in our series.

© The Author(s) 2023. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Keywords

• Angiosarcoma; Immunoscore; Molecular biology; RNA-seq