biostudies-literatureHe MNIBIB NIH HHSNIAID NIH HHSNCI NIH HHSNIAMS NIH HHSeabg2752https://www.ebi.ac.uk/biostudies/studies/S-EPMC10424698biostudies-literatureUnknown379(6633)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 CD5^hi T helper and CD8⁺ T cells; further, deletion of CD5 from T cells dampened tumor elimination in response to ICB therapy in vivScience (New York, N.Y.)CD5 expression by dendritic cells directs T cell immunity and sustains immunotherapy responses.PMC10424698R01 AI022553P50 AR080594R01 AI166313T32 CA009547P30 CA091842R01 AR075959P30 CA016042R01 AR073252R01 AR040312R01 CA245277R21 EB024767R01 AR074302White MPellegrini MSette ADonermeyer DKlechevsky EGubin MMSchutt CGarin VZhao YShah KBak RKorenfeld DFerris SSchreiber RDUlezko Antonova ALindestam Arlehamn CGorvel LJensen TIModlin RLHe MAllen PMRoussak KFields RCGray JBorcherding NLuo JTung TBhatia HIberg CADinkel SMa FfalseCD5 expression by dendritic cells directs T cell immunity and sustains immunotherapy responses.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 CD5^hi T helper and CD8⁺ T cells; further, deletion of CD5 from T cells dampened tumor elimination in response to ICB therapy in viv2023-01-01T00:00:00Z2023 Feb2026-05-28T18:44:15.46Z2025-04-06T22:00:31.869ZS-EPMC104246983679580510.1126/science.abg2752