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Cited by 1,081Immunotherapy and Immune Responsesinterferon and immune responsesCancer Immunotherapy and Biomarkers

Type I interferon is selectively required by dendritic cells for immune rejection of tumors

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Diamond, Mark S., Kinder, Michelle, Matsushita, Hirokazu, Mashayekhi, Mona, Dunn, Gavin P., Archambault, Jessica M., Lee, Hsiaoju, Arthur, Cora D. +4 more·2011·Journal of Experimental Medicine
DOI 10.1084/jem.20101158PMC PMC3182061
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Abstract

Cancer immunoediting is the process whereby the immune system suppresses neoplastic growth and shapes tumor immunogenicity. We previously reported that type I interferon (IFN-α/β) plays a central role in this process and that hematopoietic cells represent critical targets of type I IFN’s actions. However, the specific cells affected by IFN-α/β and the functional processes that type I IFN induces remain undefined. Herein, we show that type I IFN is required to initiate the antitumor response and that its actions are temporally distinct from IFN-γ during cancer immunoediting. Using mixed bone marrow chimeric mice, we demonstrate that type I IFN sensitivity selectively within the innate immune compartment is essential for tumor-specific T cell priming and tumor elimination. We further show that mice lacking IFNAR1 (IFN-α/β receptor 1) in dendritic cells (DCs; Itgax-Cre+Ifnar1f/f mice) cannot reject highly immunogenic tumor cells and that CD8α+ DCs from these mice display defects in antigen cross-presentation to CD8+ T cells. In contrast, mice depleted of NK cells or mice that lack IFNAR1 in granulocytes and macrophage populations reject these tumors normally. Thus, DCs and specifically CD8α+ DCs are functionally relevant targets of endogenous type I IFN during lymphocyte-mediated tumor rejection.

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  • Type-I IFNs are important in the initiation of spontaneous and iatrogenic antitumor immune T cell responses.

    “several preclinical studies have confirmed the important function of type-I IFNs in the initiation of spontaneous and iatrogenic antitumor immune T cell responses”

    From Epigenetic state determines the in vivo efficacy of STING agonist therapy (2023) · cites this paper as [17]

    The Results and Discussion show that type I IFN is needed early for tumor-specific cytotoxic T-cell priming and identify its role in spontaneous CD8+ T-cell responses (page not provided). The paper discusses administered IFN-α in cancer treatment, but treats its immune mechanism as uncertain and calls for future study of therapeutic responses; it does not establish initiation of iatrogenic antitumor T-cell responses. (LLM, conf=0.86)

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Authors
Diamond, M. S., Kinder, M., Matsushita, H., Mashayekhi, M., Dunn, G. P., Archambault, J. M., Lee, H., Arthur, C. D., White, J. M., Kalinke, U., Murphy, K. M., & Schreiber, R. D.
Affiliations
  • Howard Hughes Medical Institute (US)
  • Center for Experimental and Clinical Infection Research (DE)
Corresponding author
Schreiber, Robert D.
ORCID
Venue
Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
2011-09-19
Volume
208
Issue
10
Pages
1989-2003
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
DOI
10.1084/jem.20101158
PMC
PMC3182061
OpenAlex
W2134007339
Cited by
1,081
References
2
Citations by year
2026: 49 · 2025: 57 · 2024: 85 · 2023: 96 · 2022: 92 · 2021: 95 · 2020: 97 · 2019: 78 · 2018: 73 · 2017: 83 · 2016: 64 · 2015: 60 · 2014: 62 · 2013: 58 · 2012: 30
FWCI
21.57
Type
journal article
Language
en
Open access
Locations
  • The Journal of Experimental Medicine (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by-nc-sa)
  • HZI (Helmholtz Centre for Infection Research) (submittedVersion)
Funders
  • Cancer Research Institute
  • Ludwig Institute for Cancer Research
  • National Cancer Institute
  • National Institute of Allergy and Infectious Diseases
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords
type I interferon, dendritic cells, CD8α+ dendritic cells, cancer immunoediting, tumor rejection, IFNAR1, cross-presentation, natural killer cells, granulocytes, macrophages, innate immunity, antitumor immunity
MeSH terms
Animals, Chimera, Dendritic Cells, Granulocytes, Immunity, Innate, Interferon Type I, Interferon-gamma, Killer Cells, Natural, Lymphocyte Activation, Macrophages, Mice, Inbred C57BL, Neoplasms, T-Lymphocytes, Cytotoxic, T-Lymphocyte Subsets, Mice, Knockout, Adoptive Transfer, Cross-Priming, Mice, Receptor, Interferon alpha-beta

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