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“Immune system stimulation via enhanced antigen cross-presentation by reprogrammed MSCs” refers to engineering or pharmacologic licensing of mesenchymal stromal cells so they acquire or increase the capacity to cross-present exogenous antigens on MHC class I to prime CD8 T cells. Foundational studies showed murine MSCs can cross-present soluble ovalbumin to naive OT-I CD8 T cells in a proteasome- and partially TAP-dependent manner, and IFN-γ pretreatment upregulates antigen-processing/presentation pathways and boosts cross-presentation in vitro and in vivo[1]. More recently, small-molecule reprogramming with UM171a drives mitochondrial ROS, induces PSMB8, increases MHC I (H2-Kb), confers cross-presentation without IFN-γ, and enables therapeutic vaccination effects controlling tumor growth in mice[4][2]. Conversely, MSCs can suppress dendritic-cell cross-presentation and T-cell priming under some conditions, highlighting context-dependent immunobiology and safety considerations[3][5].
UM171a induces mitochondrial reactive oxygen species, upregulates immunoproteasome subunit PSMB8, increases MHC class I (H2-Kb) expression, enabling de novo antigen cross-presentation by MSCs to CD8 T cells[4][2] IFN-γ licensing increases antigen-processing/presentation machinery in MSCs, enhancing cross-presentation capacity in vitro and in vivo[1]
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