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

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.