Antigen loaded monocytes prime CD4+ T cell responses through Notch2 dependent cDC2

Abstract Cellular vaccines, primarily monocyte-derived dendritic cells (MoDC), have recently been realized as therapeutic cancer vaccines with modest clinical efficacy. Understanding the mechanism by which these lead to antigen presentation is key improving their potency. A significant advancement was discovery that MoDC do not directly present antigen, but instead rely on endogenous for presenting cell (APC) function. Subsequent research has also demonstrated primary monocytes can be loaded and used cellular outperforming in mouse models of melanoma glioblastoma. In this study, we characterized how monocyte generate CD4+ T responses. We utilized CD11c-Cre RBPJfl/flmouse model, lack a subset Notch2 dependent cDC2 expression Endothelial cell-selective adhesion molecule (ESAM hi). demonstrate ESAM hicDC2 required effective OT-II priming after vaccination ovalbumin (OVA) monocytes. Interestingly, depletion hiDC population does affect vaccine-induced CD8+ priming, process previously shown cDC1. This indicates responses independently transferring both hiand DCs, leveraging APC function prime responses, respectively. work furthers mechanistic understanding will inform design future they enter trials vaccines. Supported NCI P50 CA 190991 funding from Stead Scholarship Program Duke University Department Medicine.