Single-cell analysis reveals the stromal dynamics and tumor-specific characteristics in the microenvironment of ovarian cancer.
bioRxiv
; 2023 Jun 09.
Article
em En
| MEDLINE
| ID: mdl-37333262
ABSTRACT
High-grade serous ovarian carcinoma (HGSOC) is a heterogeneous disease, and a high stromal/desmoplastic tumor microenvironment (TME) is associated with a poor outcome. Stromal cell subtypes, including fibroblasts, myofibroblasts, and cancer-associated mesenchymal stem cells, establish a complex network of paracrine signaling pathways with tumor-infiltrating immune cells that drive effector cell tumor immune exclusion and inhibit the antitumor immune response. Single-cell transcriptomics of the HGSOC TME from public and in-house datasets revealed a distinct transcriptomic landscape for immune and non-immune cells in high-stromal vs. low-stromal tumors. High-stromal tumors had a lower fraction of certain T cells, natural killer (NK) cells, and macrophages and increased expression of CXCL12 in epithelial cancer cells and cancer-associated mesenchymal stem cells (CA-MSCs). Analysis of cell-cell communication indicated that epithelial cancer cells and CA-MSCs secreted CXCL12 that interacted with the CXCR4 receptor, which was overexpressed on NK and CD8 + T cells. CXCL12 and/or CXCR4 antibodies confirmed the immunosuppressive role of CXCL12-CXCR4 in high-stromal tumors.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article