Harnessing dendritic cells as immunological bridges to potentiate mRNA cancer vaccines

Abstract

mRNA-based cancer vaccines have emerged as a transformative immunotherapy, with dendritic cells (DCs) serving as pivotal orchestrators of innate and adaptive antitumor immunity. This review explores how DCs function as immunological bridges to enhance mRNA vaccine efficacy by integrating antigen presentation with coordinated immune cell crosstalk. We first outline the functional diversity of DC subsets, emphasizing their maturation dynamics and intrinsic potential in mRNA vaccines. Next, we discuss key advancements in mRNA vaccine development, including optimized in vitro-transcribed (IVT) mRNA constructs and delivery platforms in vivo. A central focus is the DC-mediated immune response, detailing mechanisms by which DCs prime cytotoxic CD8⁺ T cells, engage CD4⁺ T helper cells, activate B cells for humoral responses, and recruit natural killer (NK) cells for innate killing. This review highlights the current understanding of the role of DCs in enhancing mRNA cancer vaccines and provides perspectives on future research directions, aiming to improve cancer immunotherapy outcomes.