Visualizing Synaptic Transfer of Tumor Antigens among Dendritic Cells

Generation of tumor-infiltrating lymphocytes begins when tumor antigens reach the lymph node (LN) to stimulate T cells, yet we know little of how tumor material is disseminated among the large variety of antigen-presenting dendritic cell (DC) subsets in the LN. Here, we demonstrate that tumor proteins are carried to the LN within discrete vesicles inside DCs and are then transferred among DC subsets. A synapse is formed between interacting DCs and vesicle transfer takes place in the absence of free exosomes. DCs -containing vesicles can uniquely activate T cells, whereas DCs lacking them do not. Understanding this restricted sharing of tumor identity provides substantial room for engineering better anti-tumor immunity. [Display omitted] •Myeloid cells retain tumor-derived antigens in intracellular vesicles•Dynamic synapses facilitate membrane and vesicular exchange between myeloid cells•Migratory DC pass vesicular tumor antigen to resident DC at points of contact•Migratory versus resident cDC1 exhibit differential T cell priming characteristics Ruhland et al. capture a novel vesicle-encapsulated and contact-dependent transfer of tumor-derived material and antigens between dendritic cells, leading to effective and varied T cell priming in the lymph node.