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

Mingyu He; Kate Roussak; Feiyang Ma; Nicholas Borcherding; Vince Garin; Mike White; Charles Schutt; Trine I Jensen; Yun Zhao; Courtney A Iberg; Kairav Shah; Himanshi Bhatia; Daniel Korenfeld; Sabrina Dinkel; Judah Gray; Alina Ulezko Antonova; Stephen Ferris; David Donermeyer; Cecilia Lindestam Arlehamn; Matthew M Gubin; Jingqin Luo; Laurent Gorvel; Matteo Pellegrini; Alessandro Sette; Thomas Tung; Rasmus Bak; Robert L Modlin; Ryan C Fields; Robert D Schreiber; Paul M Allen; Eynav Klechevsky

doi:10.1126/science.abg2752

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

Mingyu He
, Kate Roussak
, Feiyang Ma
, Nicholas Borcherding
, Vince Garin
, Mike White
, Charles Schutt
, Trine I Jensen
, Yun Zhao
, Courtney A Iberg
, Kairav Shah
, Himanshi Bhatia
, Daniel Korenfeld
, Sabrina Dinkel
, Judah Gray
, Alina Ulezko Antonova
, Stephen Ferris
, David Donermeyer
, Cecilia Lindestam Arlehamn
, Matthew M Gubin

Jingqin Luo, Laurent Gorvel, Matteo Pellegrini, Alessandro Sette, Thomas Tung, Rasmus Bak, Robert L Modlin, Ryan C Fields, Robert D Schreiber, Paul M Allen, Eynav Klechevsky

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

92 Citationer (Scopus)

Abstract

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 vivo. Thus, CD5 + DCs are an essential component of optimal ICB therapy.

Originalsprog	Engelsk
Artikelnummer	eabg2752
Tidsskrift	Science
Vol/bind	379
Nummer	6633
Antal sider	17
ISSN	0036-8075
DOI	https://doi.org/10.1126/science.abg2752
Status	Udgivet - 17 feb. 2023

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10.1126/science.abg2752

https://pmc.ncbi.nlm.nih.gov/articles/PMC10424698/pdf/nihms-1899517.pdf

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He, M., Roussak, K., Ma, F., Borcherding, N., Garin, V., White, M., Schutt, C., Jensen, T. I., Zhao, Y., Iberg, C. A., Shah, K., Bhatia, H., Korenfeld, D., Dinkel, S., Gray, J., Ulezko Antonova, A., Ferris, S., Donermeyer, D., Lindestam Arlehamn, C., ... Klechevsky, E. (2023). CD5 expression by dendritic cells directs T cell immunity and sustains immunotherapy responses. Science, 379(6633), Artikel eabg2752. https://doi.org/10.1126/science.abg2752

@article{0a5862aa3391473b9491d06b9b57ccb2,

title = "CD5 expression by dendritic cells directs T cell immunity and sustains immunotherapy responses",

abstract = "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 vivo. Thus, CD5 + DCs are an essential component of optimal ICB therapy. ",

author = "Mingyu He and Kate Roussak and Feiyang Ma and Nicholas Borcherding and Vince Garin and Mike White and Charles Schutt and Jensen, \{Trine I\} and Yun Zhao and Iberg, \{Courtney A\} and Kairav Shah and Himanshi Bhatia and Daniel Korenfeld and Sabrina Dinkel and Judah Gray and \{Ulezko Antonova\}, Alina and Stephen Ferris and David Donermeyer and \{Lindestam Arlehamn\}, Cecilia and Gubin, \{Matthew M\} and Jingqin Luo and Laurent Gorvel and Matteo Pellegrini and Alessandro Sette and Thomas Tung and Rasmus Bak and Modlin, \{Robert L\} and Fields, \{Ryan C\} and Schreiber, \{Robert D\} and Allen, \{Paul M\} and Eynav Klechevsky",

year = "2023",

month = feb,

day = "17",

doi = "10.1126/science.abg2752",

language = "English",

volume = "379",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6633",

}

He, M, Roussak, K, Ma, F, Borcherding, N, Garin, V, White, M, Schutt, C, Jensen, TI, Zhao, Y, Iberg, CA, Shah, K, Bhatia, H, Korenfeld, D, Dinkel, S, Gray, J, Ulezko Antonova, A, Ferris, S, Donermeyer, D, Lindestam Arlehamn, C, Gubin, MM, Luo, J, Gorvel, L, Pellegrini, M, Sette, A, Tung, T, Bak, R, Modlin, RL, Fields, RC, Schreiber, RD, Allen, PM & Klechevsky, E 2023, 'CD5 expression by dendritic cells directs T cell immunity and sustains immunotherapy responses', Science, bind 379, nr. 6633, eabg2752. https://doi.org/10.1126/science.abg2752

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 - Ulezko Antonova, Alina

AU - Ferris, Stephen

AU - Donermeyer, David

AU - Lindestam Arlehamn, Cecilia

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

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 CD5 hi 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 CD5 hi 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.

UR - https://www.scopus.com/pages/publications/85148260085

U2 - 10.1126/science.abg2752

DO - 10.1126/science.abg2752

M3 - Journal article

C2 - 36795805

SN - 0036-8075

VL - 379

JO - Science

JF - Science

IS - 6633

M1 - eabg2752

ER -

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

Abstract

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