Journal
SCIENCE
Volume 379, Issue 6633, Pages 661-+Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abg2752
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The reduction of human CD1c+CD5+ dendritic cells (DCs) in melanoma-affected lymph nodes and the correlation between CD5 expression on DCs and patient survival have been observed. Activating CD5 on DCs enhances T cell priming and improves survival after immune checkpoint blockade (ICB) therapy. CD5+ DCs are essential for optimal ICB therapy.
The induction of proinflammatory T cells by dendritic cell (DC) subtypes is critical for antitumor responses and effective immune checkpoint blockade (ICB) therapy. Here, we show that human CD1c+CD5+ DCs are reduced in melanoma-affected lymph nodes, with CD5 expression on DCs correlating with patient survival. Activating CD5 on DCs enhanced T cell priming and improved survival after ICB therapy. CD5+ DC numbers increased during ICB therapy, and low interleukin-6 (IL-6) concentrations promoted their de novo differentiation. Mechanistically, CD5 expression by DCs was required to generate optimally protective CD5hi T helper and CD8+ T cells; further, deletion of CD5 from T cells dampened tumor elimination in response to ICB therapy in vivo. Thus, CD5+ DCs are an essential component of optimal ICB therapy.
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