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Science ; 379(6633): eabg2752, 2023 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-36795805

RESUMO

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.


Assuntos
Antígenos CD5 , Linfócitos T CD8-Positivos , Células Dendríticas , Inibidores de Checkpoint Imunológico , Imunoterapia , Melanoma , Linfócitos T Auxiliares-Indutores , Humanos , Linfócitos T CD8-Positivos/imunologia , Diferenciação Celular , Células Dendríticas/imunologia , Melanoma/tratamento farmacológico , Antígenos CD5/metabolismo , Inibidores de Checkpoint Imunológico/uso terapêutico , Linfócitos T Auxiliares-Indutores/imunologia
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