PGRN mediates the crosstalk between ovarian cancer cells and CAFs and reshapes tumor immune microenvironment
The tumor microenvironment (TME) serves crucial functions in ovarian cancer progression through complex interactions between tumor cells and stromal cells, particularly cancer-associated fibroblasts (CAFs). However, tumor-stroma interactions in ovarian cancer remain poorly characterized. Here, we identified progranulin (PGRN) as a key TME mediator that promotes crosstalk between tumor cells and CAFs, contributing to an immunosuppressive microenvironment. First, we discovered that PGRN deficiency in tumor cells attenuated malignant phenotypes and orthotopic tumor growth, while also suppressing CAF activation. Conversely, CAF-derived PGRN promoted tumor proliferation and invasion, while fibroblast-specific ablation of PGRN markedly suppressed tumor growth in vivo. Remarkably, PGRN in the TME rejected intratumoral CD8