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Cited by 372Immunotherapy and Immune ResponsesCancer Immunotherapy and BiomarkersT-cell and B-cell Immunology

Type I interferon activates MHC class I-dressed CD11b+ conventional dendritic cells to promote protective anti-tumor CD8+ T cell immunity

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Duong, Ellen, Fessenden, Tim B., Lutz, Emi, Dinter, Teresa, Yim, Leon, Blatt, Sarah, Bhutkar, Arjun, Wittrup, Karl Dane +1 more·2022·Immunity
DOI 10.1016/j.immuni.2021.10.020PMC PMC10827482
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Abstract

Tumor-infiltrating dendritic cells (DCs) assume varied functional states that impact anti-tumor immunity. To delineate the DC states associated with productive anti-tumor T cell immunity, we compared spontaneously regressing and progressing tumors. Tumor-reactive CD8+ T cell responses in Batf3-/- mice lacking type 1 DCs (DC1s) were lost in progressor tumors but preserved in regressor tumors. Transcriptional profiling of intra-tumoral DCs within regressor tumors revealed an activation state of CD11b+ conventional DCs (DC2s) characterized by expression of interferon (IFN)-stimulated genes (ISGs) (ISG+ DCs). ISG+ DC-activated CD8+ T cells ex vivo comparably to DC1. Unlike cross-presenting DC1, ISG+ DCs acquired and presented intact tumor-derived peptide-major histocompatibility complex class I (MHC class I) complexes. Constitutive type I IFN production by regressor tumors drove the ISG+ DC state, and activation of MHC class I-dressed ISG+ DCs by exogenous IFN-β rescued anti-tumor immunity against progressor tumors in Batf3-/- mice. The ISG+ DC gene signature is detectable in human tumors. Engaging this functional DC state may present an approach for the treatment of human disease.

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  • The importance of IFN-β production by cancer cells in the recruitment and activation of Batf3-dependent dendritic cells has been demonstrated in different settings.

    “The importance of IFN-β production by cancer cells in the recruitment and activation of Batf3-dependent dendritic cells has been also demonstrated in different settings47,49.”

    From Epigenetic state determines the in vivo efficacy of STING agonist therapy (2023) · cites this paper as [49]

    The Results section on IFN-β addition (page unavailable) reports activation and increased infiltration of ISG+ dendritic cells in Batf3−/− mice, which lack Batf3-dependent DC1s. The Discussion identifies these cells as CD11b+ DCs and says IFN-β can drive anti-tumor responses without DC1s. Thus, although the paper links tumor-derived type I interferon to dendritic-cell activation, its demonstrated mechanism is contrary to the claim that it recruits and activates Batf3-dependent dendritic cells. (LLM, conf=0.85)

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  • Two recent publications describe a novel role for cancer cells and their type I IFN production in priming CD8+ T cell responses through MHC class I dressing of dendritic cells.

    “This notion is further supported by two recent publications describing a novel role for cancer cells and their type I IFN production in priming CD8+ T cell responses through MHC class I dressing of dendritic cells49,62.”

    From Epigenetic state determines the in vivo efficacy of STING agonist therapy (2023) · cites this paper as [49]

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Sorted by citations

Authors
Duong, E., Fessenden, T. B., Lutz, E., Dinter, T., Yim, L., Blatt, S., Bhutkar, A., Wittrup, K. D., & Spranger, S.
Affiliations
  • Koch Institute for Integrative Cancer Research At MIT (US)
  • Ragon Institute of MGH, MIT and Harvard (US)
Corresponding author
Spranger, Stefani
ORCID
Venue
Immunity
Publisher
Elsevier BV
Published
2022-02
Volume
55
Issue
2
Pages
308-323.e9
ISSN
1074-7613 (ISSN-L)
DOI
10.1016/j.immuni.2021.10.020
PMC
PMC10827482
OpenAlex
W3216766978
Cited by
372
References
18
Citations by year
2026: 77 · 2025: 87 · 2024: 92 · 2023: 68 · 2022: 48
FWCI
19.40
Type
journal article
Language
en
Open access
Licence
Locations
  • Immunity (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (T32GM007287)
  • PEW Charitable Trusts
  • National Cancer Institute (P30 CA014051-49)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
type I interferon, MHC class I, tumor-infiltrating dendritic cells, CD8+ T cell immunity, antitumor immunity, interferon-stimulated genes, Batf3, tumor regression, tumor progression, cross-presentation, interferon-beta
MeSH terms
Animals, Antigens, Neoplasm, Dendritic Cells, Interferon Type I, Neoplasms, Histocompatibility Antigens Class I, Signal Transduction, Lymphocytes, Tumor-Infiltrating, Interferon-beta, Receptors, Interferon, CD8-Positive T-Lymphocytes, CD11b Antigen, Cross-Priming, Mice, Tumor Microenvironment

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