Distinctive histogenesis and immunological microenvironment based on transcriptional profiles of Follicular dendritic cell sarcomas

Maria Antonella Laginestra, Claudio Tripodo, Claudio Agostinelli, Giovanna Motta, Sylvia Hartmann, Claudia Döring, Maura Rossi, Federica Melle, Maria Rosaria Sapienza, Valentina Tabanelli, Alessandro Pileri, Fabio Fuligni, Anna Gazzola, Claudia Mannu, Carlo Alberto Sagramoso, Silvia Lonardi, Luisa Lorenzi, Francesco Bacci, Elena Sabattini, Anita BorgesIngrid Simonitsch-Klupp, Jose Cabecadas, Elias Campo, Juan Rosai, Martin Leo Hansmann, Fabio Facchetti, Stefano Aldo Pileri

Research output: Contribution to journalArticle

Abstract

Follicular dendritic cell (FDC) sarcomas are rare mesenchymal tumors with variable clinical, morphologic, and phenotypic characteristics. Transcriptome analysis was performed on multiple FDC sarcomas and compared with other mesenchymal tumors, microdissected Castleman FDCs, and normal fibroblasts. Using unsupervised analysis, FDC sarcomas clustered with microdissected FDCs, distinct from other mesenchymal tumors and fibroblasts. The specific endowment of FDC-related gene expression programs in FDC sarcomas emerged by applying a gene signature of differentially expressed genes (n = 1,289) between microdissected FDCs and fibroblasts. Supervised analysis comparing FDC sarcomas with microdissected FDCs and other mesenchymal tumors identified 370 and 2,927 differentially expressed transcripts, respectively, and on the basis of pathway enrichment analysis ascribed to signal transduction, chromatin organization, and extracellular matrix organization programs. As the transcriptome of FDC sarcomas retained similarity with FDCs, the immune landscape of FDC sarcoma was investigated by applying the CIBERSORT algorithm to FDC sarcomas and non-FDC mesenchymal tumors and demonstrated that FDC sarcomas were enriched in T follicular helper (Tfh) and T regulatory (Treg) cell populations, as confirmed in situ by immunohistochemistry. The enrichment in specific T-cell subsets prompted investigating the mRNA expression of the inhibitory immune receptor PD-1 and its ligands PD-L1 and PD-L2, which were found to be significantly upregulated in FDC sarcomas as compared with other mesenchymal tumors, a finding also confirmed in situ. Here, it is demonstrated for the first time the transcriptional relationship of FDC sarcomas with nonmalignant FDCs and their distinction from other mesenchymal tumors.

Original languageEnglish
Pages (from-to)541-552
Number of pages12
JournalMolecular Cancer Research
Volume15
Issue number5
DOIs
Publication statusPublished - May 1 2017

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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  • Cite this

    Laginestra, M. A., Tripodo, C., Agostinelli, C., Motta, G., Hartmann, S., Döring, C., Rossi, M., Melle, F., Sapienza, M. R., Tabanelli, V., Pileri, A., Fuligni, F., Gazzola, A., Mannu, C., Sagramoso, C. A., Lonardi, S., Lorenzi, L., Bacci, F., Sabattini, E., ... Pileri, S. A. (2017). Distinctive histogenesis and immunological microenvironment based on transcriptional profiles of Follicular dendritic cell sarcomas. Molecular Cancer Research, 15(5), 541-552. https://doi.org/10.1158/1541-7786.MCR-16-0301