Visualizing Synaptic Transfer of Tumor Antigens Amongst Dendritic Cells

Abstract

Tumors frequently program CD8 T cell immunity that is ‘exhausted’, or otherwise fails to provide for tumor clearance. This begins when tumor antigens reach the lymph node (LN) to stimulate T cells yet we know little of how tumor material is transported and disseminated amongst the large variety of antigen-presenting dendritic cell (DC) subsets in the LN.  Here, in vitro and in vivo assays together with lattice light sheet and multiphoton imaging we demonstrate that tumor proteins are carried to LN within discrete vesicles inside DC and are then transferred amongst DC subsets. A cup-on-cup synapse is formed between interacting DC and directed vesicle transfer takes place routinely in the absence of free exosomes. DC containing these vesicles can uniquely activate T cells whereas DC lacking them do not. Understanding this restricted sharing of tumor identity provides substantial room for engineering better anti-tumor immunity.

Keywords: dendritic cells, CD8+ T cells, Tumor Immunology, antigen trafficking, lymph node, T cell priming, antigen presentation