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cDC1 prime and are licensed by CD4(+) T cells to induce anti-tumour immunity
Open accessAbstract
Conventional type 1 dendritic cells (cDC1)1 are thought to perform antigen cross-presentation, which is required to prime CD8+ T cells 2,3, whereas cDC2 are specialized for priming CD4+ T cells 4,5. CD4+ T cells are also considered to help CD8+ T cell responses through a variety of mechanisms 6-11, including a process whereby CD4+ T cells 'license' cDC1 for CD8+ T cell priming 12. However, this model has not been directly tested in vivo or in the setting of help-dependent tumour rejection. Here we generated an Xcr1 Cre 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.
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“cDC1 are critical for antigen cross-presentation required to prime CD8+ T cells for optimal anti-tumor immunity and priming of CD4+ T cells at early stages, partly because cDC1 provides antigen transportation to lymph nodes for processing by cDC2 (36).”
From mRNA vaccine with unmodified uridine induces robust type I interferon-dependent anti-tumor immunity in a melanoma model (2022) · cites this paper as [36]
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“CD40 signaling in cDC1 is required for tumor rejection by playing a key role in augmenting the proliferation of antigen-specific CD8+ T cells (36).”
From mRNA vaccine with unmodified uridine induces robust type I interferon-dependent anti-tumor immunity in a melanoma model (2022) · cites this paper as [36]
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Metadata
- Authors
- Ferris, S. T., Durai, V., Wu, R., Theisen, D. J., Ward, J. P., Bern, M. D., Davidson, J. T., Bagadia, P., Liu, T., Briseño, C. G., Li, L., Gillanders, W. E., Wu, G. F., Yokoyama, W. M., Murphy, T. L., Schreiber, R. D., & Murphy, K. M.
- Affiliations
- Washington University in St. Louis (US)
- University of California, San Francisco (US)
- Barnes-Jewish Hospital (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Murphy, Kenneth M.
- ORCID
- Venue
- Nature
- Published
- 2020-08-12
- Volume
- 584
- Issue
- 7822
- Pages
- 624-629
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC7469755
- OpenAlex
- W3048641542
- Cited by
- 611
- References
- 50
- Citations by year
- 2026: 112 · 2025: 105 · 2024: 112 · 2023: 127 · 2022: 76 · 2021: 67 · 2020: 12
- FWCI
- 24.74
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (UL1TR000448, UL1TR002345)
- National Cancer Institute (T32CA009573, R01CA190700, T32CA009621, R01CA248919, P30CA091842)
- National Institute of Allergy and Infectious Diseases (R01AI150297, R01AI129545, T32AI007163, R01AI162643)
- National Institute of Diabetes and Digestive and Kidney Diseases (F30DK108498, F30DK112466)
- National Institute of Neurological Disorders and Stroke (R01NS106289)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30AR073752)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- conventional type 1 dendritic cells, cDC1, CD4+ T cell priming, CD8+ T cell priming, MHC class II, MHC class I, cross-presentation, tumor rejection, antitumor immunity
- MeSH terms
- Animals, Histocompatibility Antigens Class II, Dendritic Cells, Female, Neoplasms, Signal Transduction, CD4-Positive T-Lymphocytes, Antigen Presentation, CD8-Positive T-Lymphocytes, CD40 Antigens, Cross-Priming, Mice
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