CD5 expression by dendritic cells directs T cell immunity and sustains immunotherapy responses

• 成果类型: Article
• 署名作者: He, Mingyu; Roussak, Kate; Ma, Feiyang; Borcherding, Nicholas; Garin, Vince; White, Mike; Schutt, Charles; Jensen, Trine I.; Zhao, Yun; Iberg, Courtney A.; Shah, Kairav; Bhatia, Himanshi; Korenfeld, Daniel; Dinkel, Sabrina; Gray, Judah; Antonova, Alina Ulezko; Ferris, Stephen; Donermeyer, David; Arlehamn, Cecilia Lindestam; Gubin, Matthew M.; Luo, Jingqin; Gorvel, Laurent; Pellegrini, Matteo; Sette, Alessandro; Tung, Thomas; Bak, Rasmus; Modlin, Robert L.; Fields, Ryan C.; Schreiber, Robert D.; Allen, Paul M.; Klechevsky, Eynav
• 署名单位: Washington University (WUSTL); University of California System; University of California Los Angeles; Aarhus University; La Jolla Institute for Immunology; Washington University (WUSTL); University of California System; University of California San Diego; Washington University (WUSTL); Aarhus University; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-10487
• DOI: 10.1126/science.abg2752
• 发表日期: 2023-02-17
• 页码: 661-+
• 关键词: human langerhans cells; human cord blood; signal-transduction; negative regulation; analysis reveals; gene-expression; surface; ligand; activation; subsets

摘要

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.