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. GubinJingqin 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

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

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.

Original language	English (US)
Article number	eabg2752
Journal	Science
Volume	379
Issue number	6633
DOIs	https://doi.org/10.1126/science.abg2752
State	Published - Feb 17 2023
Externally published	Yes

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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., Antonova, A. U., Ferris, S., Donermeyer, D., Arlehamn, C. L., ... Klechevsky, E. (2023). CD5 expression by dendritic cells directs T cell immunity and sustains immunotherapy responses. Science, 379(6633), Article eabg2752. https://doi.org/10.1126/science.abg2752

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, Antonova, AU, Ferris, S, Donermeyer, D, Arlehamn, CL, 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, vol. 379, no. 6633, eabg2752. https://doi.org/10.1126/science.abg2752

@article{f9330e83360f4b209e921394b9d9a107,

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 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.",

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 Antonova, {Alina Ulezko} and Stephen Ferris and David Donermeyer and Arlehamn, {Cecilia Lindestam} 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",

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day = "17",

doi = "10.1126/science.abg2752",

language = "English (US)",

volume = "379",

journal = "Science",

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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

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

Abstract

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