MnO2 nanoparticle improves the immunosuppressive characteristics of tumor-associated mesenchymal stromal cells

Abstract

Tumor-associated marrow mesenchymal stem/stromal cells have immunosuppressive effects on immune cells within the tumor microenvironment in various cancers. However, effective treatments targeting these cells are currently limited. Here, we developed a nanoparticle of MnO2 aiming to inhibit the immunosuppressive properties of Tumor-Associated Marrow Mesenchymal stem/stromal cells. We investigated the physicochemical characteristics of MnO2 and its potential for alleviating hypoxia in IL17 and IFNγ transformed Tumor-Associated Marrow Mesenchymal stem/stromal cells. The Tumor-Associated Marrow Mesenchymal stem/stromal cells had higher expression level of chemokines and immunosuppressors, which promotes the progression of tumors and inhibits the immune cells, leading to tumor metastasis and angiogenesis. After treatment of the nanoparticle of MnO2, the expression level of chemokines had significantly decreased due to the unique properties of MnO2. Furthermore, the nanoparticle decreased the expression level of immunosuppressors of Tumor-Associated Marrow Mesenchymal stem/stromal cells and rescued the proliferation of T lymphocytes cocultured with the cells. In conclusion, our findings demonstrate that MnO2 nanoparticles effectively improve the hypoxic microenvironment and alleviate immunosuppression caused by Tumor-Associated Marrow Mesenchymal stem/stromal cells. The utilization of this novel approach exhibits promising potential as a therapeutic strategy for addressing diverse types of cancers.