Regulation and Dysregulation of Disease Specific Immune Responses by Human Dendritic Cell Subset

Abstract Text: Dendritic cells (DCs) are key antigen-presenting cells that control both immunity and tolerance. Understanding
the principles by which DC controls these responses has provided a rich basis for studying and improving
clinical outcomes in treating human diseases. Part of the complexity is due to the existence of distinct DC
subsets, each bearing different microbial receptors, surface molecules and cytokine expression. The biological
raison d’être for separate DC subsets has been the focus of many studies, including ours. Our research focuses
on skin-migrated DC2 lineage cells, specifically on two subtypes differentiated by CD5 expression. The CD5+
DCs are highly efficient at priming cytotoxic CD8+ T cells and induce inflammatory T helper cell responses
They are elevated levels in inflamed psoriatic skin plaques, where high effector T cell responses are seen, and are reduced in malignant tissues and correlate with cancer patient survival. Consistent with this notion, we demonstrate, using human patient cells and mouse models, that
CD5 functions to trigger an inflammatory pathway of DC maturation and T cell activation. Deletion of
CD5 on DCs reduces tumor rejection and Immune checkpoint blockade (ICB) immunotherapy response. During
successful ICB immunotherapy, CD5+ DCs increased, supporting their interaction with CD5hi T
cells. New data on the differentiation of this unique DC type will be presented. Overall, our studies
highlight the role of CD5-expressing DCs in immune regulation. They provide insight into how
immunotherapies like ICB work and identify CD5 on DCs as a new potential target for enhancing response
rates among patients undergoing treatments.