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bioRxiv · 10.1101/2023.06.07.544095

Single-cell analysis reveals the stromal dynamics and tumor-specific characteristics in the microenvironment of ovarian cancer

Zhang, L.·Cascio, S.·ellors, J. W.·Buckanovich, R. J.·Osmanbeyoglu, H. U.
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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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Zhang, L., Cascio, S., ellors, J. W., Buckanovich, R. J., Osmanbeyoglu, H. U.. 2023-06-09. Single-cell analysis reveals the stromal dynamics and tumor-specific characteristics in the microenvironment of ovarian cancer. https://doi.org/10.1101/2023.06.07.544095

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