세미나

Strategies to potentiate T cells within the TME using engineered MSCs

Tumor cells interact with surrounding immune and stromal cells to create a tumor microenvironment (TME) that promotes cancer growth. As cancer progresses, the TME becomes more immunosuppressive, leading to a marked decrease in both the quantity and functionality of tumor-infiltrating lymphocytes (TILs). To counter this, immunotherapies such as immune checkpoint blockade (ICB) and cytokine therapy have been explored. However, their effectiveness is limited in advanced solid tumors, and therapeutic doses often cause severe toxicity. Mesenchymal stem cells (MSCs), which are known for their tumor-tropic properties, offer a promising platform for delivering therapeutics directly to the TME. In this study, we demonstrate that newly engineered MSCs act as potent cellular therapies, enabling precise, adjustable delivery of cytokines and immune-activating molecules into the TME. This targeted therapeutic delivery reshapes the TME, reinvigorating CD8+ TILs and enhancing anti-tumor immune responses. Furthermore, MSC-mediated TME remodeling overcomes resistance to ICB and potentiates adoptive T cell transfer (ACT), including chimeric antigen receptor (CAR) T cell therapy, in advanced solid tumors. Overall, this next-generation MSC therapy provides a novel approach to improving the TME, reinvigorating CD8+ TILs, and potentiating the efficacy of ICB and ACT therapies.