TY - JOUR
T1 - CD5 expression by dendritic cells directs T cell immunity and sustains immunotherapy responses
AU - He, Mingyu
AU - Roussak, Kate
AU - Ma, Feiyang
AU - Borcherding, Nicholas
AU - Garin, Vince
AU - White, Mike
AU - Schutt, Charles
AU - Jensen, Trine I.
AU - Zhao, Yun
AU - Iberg, Courtney A.
AU - Shah, Kairav
AU - Bhatia, Himanshi
AU - Korenfeld, Daniel
AU - Dinkel, Sabrina
AU - Gray, Judah
AU - Antonova, Alina Ulezko
AU - Ferris, Stephen
AU - Donermeyer, David
AU - Arlehamn, Cecilia Lindestam
AU - Gubin, Matthew M.
AU - Luo, Jingqin
AU - Gorvel, Laurent
AU - Pellegrini, Matteo
AU - Sette, Alessandro
AU - Tung, Thomas
AU - Bak, Rasmus
AU - Modlin, Robert L.
AU - Fields, Ryan C.
AU - Schreiber, Robert D.
AU - Allen, Paul M.
AU - Klechevsky, Eynav
N1 - Publisher Copyright:
© 2023 American Association for the Advancement of Science. All rights reserved.
PY - 2023/2/17
Y1 - 2023/2/17
N2 - 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.
AB - 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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U2 - 10.1126/science.abg2752
DO - 10.1126/science.abg2752
M3 - Article
C2 - 36795805
AN - SCOPUS:85148260085
SN - 0036-8075
VL - 379
JO - Science
JF - Science
IS - 6633
M1 - eabg2752
ER -