Distinctive Histogenesis and Immunological Microenvironment Based on Transcriptional Profiles of Follicular Dendritic Cell Sarcomas

ABSTRACT: Follicular dendritic cell (FDC) sarcomas are rare mesenchymal tumours (MTs) with variable clinical, morphologic and phenotypic characteristics. We investigated the transcriptome of 29 FDC sarcomas and compared it with that of other MTs, microdissected Castleman FDCs, and normal fibroblasts. On unsupervised analysis, FDC sarcoma clustered with microdissected FDCs, distinct from other MTs and fibroblasts. The specific endowment of FDC-related programs in FDC sarcomas emerged by applying a gene signature consisting of 1,289 genes differentially expressed between microdissected FDCs and fibroblasts. Supervised analysis comparing FDC sarcomas with microdissected FDCs and other MTs identified 370 and 2,927 differentially expressed transcripts, respectively, which pathway enrichment analysis mainly ascribed to signal transduction, chromatin organization, and extracellular matrix organization programs. Since the transcriptome of FDC sarcomas retained similarity with that of FDCs, we investigated the immune landscape of FDC sarcoma by applying the CIBERSORT analysis to FDC sarcomas and non-FDC MTs, and demonstrated that FDC sarcomas were enriched in TFH and TREG 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 of its ligands PD-L1 and PD-L2, which were found to be significantly more expressed in FDC sarcomas as compared with other MTs, a finding also confirmed in situ. We demonstrated for the first time the transcriptional relationship of FDC sarcomas with non-malignant FDCs and their distinction from other MTs. Furthermore, we provided evidence of a peculiar immunological microenvironment associated with FDC sarcomas.

ORGANISM(S): Homo sapiens

PROVIDER: GSE90592 | GEO | 2017/04/07

SECONDARY ACCESSION(S): PRJNA355130

REPOSITORIES: GEO