Dataset Information

Stromal-immune interactions promote immune suppression in intraperitoneal metastasis of ovarian carcinoma

ABSTRACT: High-grade serous (tubo-ovarian) carcinoma (HGSC) is the most lethal gynecological malignancy and the most common form of ovarian cancer. Most patients (75%) are diagnosed at advanced disease stages, with widespread peritoneal dissemination leading to poor prognosis. Cancer-associated fibroblasts (CAFs) were shown to modulate the immune microenvironment in multiple cancer types. However, their interactions with immune cells and their role in facilitating peritoneal metastasis in ovarian cancer are largely unresolved. Here, we characterized the interactions between fibroblasts and immune cells that facilitate the formation of a hospitable niche in metastatic peritoneal ovarian cancer. We isolated and characterized CAFs from HGSC patients and mouse models, and investigated the events that promote peritoneal metastases. Our findings reveal the reciprocal communication between fibroblasts and T cells in distinct peritoneal metastatic niches, positioning the TIGIT-CD155 immune checkpoint signaling axis as a target for therapeutic intervention in metastatic HGSC. Our study provides a potential novel avenue for therapeutic intervention to inhibit metastatic spread of ovarian carcinoma.

ORGANISM(S): Mus musculus

PROVIDER: GSE333880 | GEO | 2026/06/11

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Background: Transcoelomic spread is the major route of metastasis of ovarian high-grade serous carcinoma (HGSC) with the omentum as the major metastatic site. Its unique tumor microenvironment with its large populations of adipocytes, mesothelial cells and immune cells establishes an intercellular signaling network that is instrumental for metastatic growth yet poorly understood. Methods: Based on transcriptomic analysis of tumor cells, tumor-associated immune and stroma cells we defined intercellular signaling pathways for 284 cytokines and growth factors and their cognate receptors after bioinformatic adjustment for contaminating cell types. The significance of individual components of this network was validated by analyzing clinical correlations and potentially pro-metastatic functions, including tumor cell migration, pro-inflammatory signal transduction and TAM expansion. Results: The data show an unexpected prominent role of host cells, and in particular of omental adipocytes, mesothelial cells and fibroblasts (CAF), in sustaining this signaling network. These cells, rather than tumor cells, are the major source of most cytokines and growth factors in the omental microenvironment (n=176 versus n=13). Many of these factors target tumor cells, are linked to metastasis and are associated with a short survival. Likewise, tumor stroma cells play a major role in both extracellular-matrix-triggered and lipid-mediated signaling. We have verified the functional significance of our observations for three exemplary instances. We show that the omental microenvironment (i) stimulates tumor cell migration via WNT4 which is highly expressed by CAF; (ii) induces pro-tumorigenic TAM proliferation in conjunction with high CSF1 expression by omental stroma cells and (iii) triggers pro-inflammatory signaling, at least in part via a HSP70 – NFkB pathway. Conclusions: The intercellular signaling network of omental metastases is majorly dependent on factors secreted by immune and stroma cells to provide an environment that supports ovarian HGSC progression. Clinically relevant pathways within this network represent novel options for therapeutic intervention.

Dataset Information

Stromal-immune interactions promote immune suppression in intraperitoneal metastasis of ovarian carcinoma

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets