ArticleStem cell research & therapy2026
Multi-armored mesenchymal stem cells potentiate antitumor immunity to combat ovarian cancer.
Article in Stem cell research & therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundOvarian cancer (OC) remains one of the most lethal gynecologic malignancies often resistant to immune checkpoint blockade (ICB) due to poor infiltration of cytotoxic CD8⁺ T cells and type 1 conventional dendritic cells (cDC1s) into the tumor microenvironment (TME). To overcome this, we engineered magnetic resonance imaging (MRI)-visible mesenchymal stem cells (MSCs) to co-express interleukin-15 (IL-15) for T-cell activation and XC motif chemokine ligand 1 (XCL1) for cDC1 recruitment, aiming to remodel the TME and enhance therapeutic outcomes.
methodsMSCs were engineered via lentiviral transduction to stably express Il15, Xcl1, and a ferritin reporter for MRI tracking. In vitro validation included assays for gene expression, cytokine secretion, T-cell proliferation, and DC migration. Therapeutic efficacy was evaluated in subcutaneous (ID8) and disseminated (intraperitoneal FLUC-eGFP-ID8 and intra-omental FLUC-eGFP-OVHM) murine OC models. Mice received peritumoral (subcutaneous model) or intraperitoneal (disseminated models) injections of engineered MSCs (1×10
resultsEngineered MSCs sustainably secreted IL‑15 and XCL1, enhancing T cell proliferation and cDC1 migration in vitro. In vivo MRI confirmed efficient MSCs homing to subcutaneous tumors, suppressing tumor growth. In disseminated models, multi-armored MSC therapy inhibited tumor progression and prolonged survival, with combination therapy achieving superior outcomes. Mechanistically, this treatment drove a robust infiltration of CD8⁺ T cells and cDC1s into the TME. Flow cytometry revealed a beneficial shift in the CD8⁺ T-cell compartment toward progenitor-like, proliferative, and effector phenotypes. Furthermore, tumor-infiltrating cDC1s displayed elevated expression of co-stimulatory molecules CD80 and CD86, indicating enhanced activation.
conclusionsMRI-visible MSCs co-expressing IL-15 and XCL1 effectively target ovarian tumors and remodel the immune microenvironment to foster potent anti-tumor immunity. By recruiting activated cDC1s and promoting durable, functional CD8⁺ T-cell responses, these multi-armored MSCs synergize with ICB to overcome therapeutic resistance. This cellular immunotherapy represents a promising strategy for ICB-resistant OC and warrants clinical translation.
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