GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE293nnn/GSE293800/primaryOK200OtherHomo sapiensOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE293800GEOGSEfalseCancer agnostic potential of CAR T cells targeting the urokinase plasminogen activator receptorChimeric Antigen Receptor (CAR) T cells have demonstrated transformative efficacy in hematologic malignancies and have shown promise in non-cancer contexts such as autoimmune diseases. We previously identified the urokinase plasminogen activator receptor (uPAR) as a cell-surface protein expressed on subsets of myeloid cells and broadly upregulated in senescent states. Murine uPAR-targeting CAR T cells can ameliorate fibrosis and prophylactically prevent metabolic syndrome in aged mice, paving the way for their use in senescence-driven pathologies. uPAR can also be expressed at high levels in cancer and, by performing a pan-cancer analysis, we now show that subsets of most tumor types display strong uPAR expression, which correlates with an epithelial-mesenchymal transition (EMT)-like state, increased fibrosis, metastasis, and poor patient outcomes. Single-cell and spatial analyses revealed that tumors with high uPAR expression in tumor cells often harbor senescent-like, uPAR-positive stromal cells, typically subsets of fibroblasts and macrophages. In mouse models, CAR T cells with uPAR-targeting single-chain variable fragments (scFvs) showed potent and persistent efficacy against multiple tumor types. In the context of high-grade serous ovarian cancer, adjuvant CAR T cell treatment following primary tumor debulking surgery cured mice by eliminating distal organ metastases. uPAR CAR T cells were well-tolerated, demonstrating efficacy in syngeneic and humanized immune system models without significant disruption of the myeloid compartment. Beyond direct tumor targeting, uPAR facilitated non-invasive cancer monitoring via soluble uPAR and PET imaging. Senescence-inducing therapies further enhanced uPAR expression and showed combinatorial activity with uPAR CAR T cells. These findings establish uPAR CAR T cells as a cancer-agnostic therapeutic strategy with a favorable safety profile and clear clinical potential in oncology, including solid tumors harboring a fibrotic tumor microenvironment linked to accumulation of senescent stromal cells.2026/03/31GSE293800GSM889021433762293800Homo sapiens