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cDC1 prime and are licensed by CD4+ T cells to induce anti-tumour immunity

Author

Listed:
  • Stephen T. Ferris

    (Washington University School of Medicine)

  • Vivek Durai

    (Washington University School of Medicine
    University of California, San Francisco)

  • Renee Wu

    (Washington University School of Medicine)

  • Derek J. Theisen

    (Washington University School of Medicine)

  • Jeffrey P. Ward

    (Washington University School of Medicine
    Washington University School of Medicine)

  • Michael D. Bern

    (Washington University School of Medicine)

  • Jesse T. Davidson

    (Washington University School of Medicine
    Washington University School of Medicine)

  • Prachi Bagadia

    (Washington University School of Medicine)

  • Tiantian Liu

    (Washington University School of Medicine)

  • Carlos G. Briseño

    (Washington University School of Medicine)

  • Lijin Li

    (Washington University School of Medicine)

  • William E. Gillanders

    (Washington University School of Medicine
    The Alvin J. Siteman Cancer Center at Barnes–Jewish Hospital and Washington University School of Medicine)

  • Gregory F. Wu

    (Washington University School of Medicine
    Washington University School of Medicine)

  • Wayne M. Yokoyama

    (Washington University School of Medicine)

  • Theresa L. Murphy

    (Washington University School of Medicine)

  • Robert D. Schreiber

    (Washington University School of Medicine
    Washington University School of Medicine
    Parker Institute for Cancer Immunotherapy)

  • Kenneth M. Murphy

    (Washington University School of Medicine
    Washington University School of Medicine)

Abstract

Conventional type 1 dendritic cells (cDC1)1 are thought to perform antigen cross-presentation, which is required to prime CD8+ T cells2,3, whereas cDC2 are specialized for priming CD4+ T cells4,5. CD4+ T cells are also considered to help CD8+ T cell responses through a variety of mechanisms6–11, including a process whereby CD4+ T cells ‘license’ cDC1 for CD8+ T cell priming12. However, this model has not been directly tested in vivo or in the setting of help-dependent tumour rejection. Here we generated an Xcr1Cre mouse strain to evaluate the cellular interactions that mediate tumour rejection in a model requiring CD4+ and CD8+ T cells. As expected, tumour rejection required cDC1 and CD8+ T cell priming required the expression of major histocompatibility class I molecules by cDC1. Unexpectedly, early priming of CD4+ T cells against tumour-derived antigens also required cDC1, and this was not simply because they transport antigens to lymph nodes for processing by cDC2, as selective deletion of major histocompatibility class II molecules in cDC1 also prevented early CD4+ T cell priming. Furthermore, deletion of either major histocompatibility class II or CD40 in cDC1 impaired tumour rejection, consistent with a role for cognate CD4+ T cell interactions and CD40 signalling in cDC1 licensing. Finally, CD40 signalling in cDC1 was critical not only for CD8+ T cell priming, but also for initial CD4+ T cell activation. Thus, in the setting of tumour-derived antigens, cDC1 function as an autonomous platform capable of antigen processing and priming for both CD4+ and CD8+ T cells and of the direct orchestration of their cross-talk that is required for optimal anti-tumour immunity.

Suggested Citation

  • Stephen T. Ferris & Vivek Durai & Renee Wu & Derek J. Theisen & Jeffrey P. Ward & Michael D. Bern & Jesse T. Davidson & Prachi Bagadia & Tiantian Liu & Carlos G. Briseño & Lijin Li & William E. Gillan, 2020. "cDC1 prime and are licensed by CD4+ T cells to induce anti-tumour immunity," Nature, Nature, vol. 584(7822), pages 624-629, August.
  • Handle: RePEc:nat:nature:v:584:y:2020:i:7822:d:10.1038_s41586-020-2611-3
    DOI: 10.1038/s41586-020-2611-3
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    Citations

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    Cited by:

    1. Diego Calzada-Fraile & Salvador Iborra & Marta Ramírez-Huesca & Inmaculada Jorge & Enrico Dotta & Elena Hernández-García & Noa Martín-Cófreces & Estanislao Nistal-Villán & Esteban Veiga & Jesús Vázque, 2023. "Immune synapse formation promotes lipid peroxidation and MHC-I upregulation in licensed dendritic cells for efficient priming of CD8+ T cells," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Lucía López & Luciano Gastón Morosi & Federica Terza & Pierre Bourdely & Giuseppe Rospo & Roberto Amadio & Giulia Maria Piperno & Valentina Russo & Camilla Volponi & Simone Vodret & Sonal Joshi & Fran, 2024. "Dendritic cell-targeted therapy expands CD8 T cell responses to bona-fide neoantigens in lung tumors," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    3. Xin Lei & Indu Khatri & Tom Wit & Iris Rink & Marja Nieuwland & Ron Kerkhoven & Hans Eenennaam & Chong Sun & Abhishek D. Garg & Jannie Borst & Yanling Xiao, 2023. "CD4+ helper T cells endow cDC1 with cancer-impeding functions in the human tumor micro-environment," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. Jae Eun Choi & Yuanyuan Qiao & Ilona Kryczek & Jiali Yu & Jonathan Gurkan & Yi Bao & Mahnoor Gondal & Jean Ching-Yi Tien & Tomasz Maj & Sahr Yazdani & Abhijit Parolia & Houjun Xia & JiaJia Zhou & Shua, 2024. "PIKfyve, expressed by CD11c-positive cells, controls tumor immunity," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    5. Denise Lau & Sonal Khare & Michelle M. Stein & Prerna Jain & Yinjie Gao & Aicha BenTaieb & Tim A. Rand & Ameen A. Salahudeen & Aly A. Khan, 2022. "Integration of tumor extrinsic and intrinsic features associates with immunotherapy response in non-small cell lung cancer," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    6. Kieran English & Rain Kwan & Lauren E. Holz & Claire McGuffog & Jelte M. M. Krol & Daryan Kempe & Tsuneyasu Kaisho & William R. Heath & Leszek Lisowski & Maté Biro & Geoffrey W. McCaughan & David G. B, 2024. "A hepatic network of dendritic cells mediates CD4 T cell help outside lymphoid organs," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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