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Cited by 720Immunotherapy and Immune Responsesinterferon and immune responsesCancer Immunotherapy and Biomarkers

STING agonist formulated cancer vaccines can cure established tumors resistant to PD-1 blockade

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Fu, Juan, Kanne, David B., Leong, Meredith, Glickman, Laura Hix, McWhirter, Sarah M., Lemmens, Edward, Mechette, Ken, Leong, Justin J. +11 more·2015·Science Translational Medicine
DOI 10.1126/scitranslmed.aaa4306PMC PMC4504692
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Abstract

Cyclic dinucleotide formulated cancer vaccine combined with PD-1 blockade can induce regression of tumors that do not express PD-L1 constitutively.

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Crossref · 10.1126/scitranslmed.aaa4306

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  • In host dendritic cells, STING-mediated IFN-β induction is essential for their activation and the cross-priming of cytotoxic T cells.

    “In host dendritic cells, STING-mediated IFN-β induction has been well characterized and shown to be essential for their activation and the cross-priming of cytotoxic T cells22,23.”

    From Epigenetic state determines the in vivo efficacy of STING agonist therapy (2023) · cites this paper as [23]

    The Results section (‘Synthetic CDN derivatives have potent human immunostimulatory capacity’; page unavailable) reports that STING agonists stimulated type I interferon production and activation markers in dendritic cells. The Discussion (page unavailable) says the mechanism by which the vaccine activates recruited dendritic cells remains to be investigated. The paper does not establish that IFN-β induction is essential for dendritic-cell activation or for cross-priming cytotoxic T cells. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

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Research works printed but not linked: 40

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Authors
Fu, J., Kanne, D. B., Leong, M., Glickman, L. H., McWhirter, S. M., Lemmens, E., Mechette, K., Leong, J. J., Lauer, P., Liu, W., Sivick, K. E., Zeng, Q., Soares, K. C., Zheng, L., Portnoy, D. A., Woodward, J. J., Pardoll, D. M., Dubensky, T. W., & Kim, Y.
Affiliations
  • Johns Hopkins University (US)
  • Aduro BioTech (United States) (US)
  • Aduro Biotech Inc., Berkeley, CA 94710, USA.
  • University of California, Berkeley (US)
  • University of Washington (US)
Corresponding author
  • Dubensky, Thomas W.
  • Kim, Young
ORCID
Venue
Science Translational Medicine
Publisher
American Association for the Advancement of Science (AAAS)
Published
2015-04-15
Volume
7
Issue
283
Pages
283ra52-283ra52
ISSN
  • 1946-6234 (ISSN-L)
  • 1946-6242
DOI
10.1126/scitranslmed.aaa4306
PMC
PMC4504692
OpenAlex
W2148482462
Cited by
720
References
4
Citations by year
2026: 36 · 2025: 52 · 2024: 72 · 2023: 67 · 2022: 68 · 2021: 82 · 2020: 90 · 2019: 83 · 2018: 60 · 2017: 65 · 2016: 33 · 2015: 12
FWCI
28.11
Type
journal article
Language
en
Open access
Licence
www.sciencemag.org/about/science-licenses-journal-article-reuse (vor, 366 d)
Locations
  • Science Translational Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • NIH (R01 CA178613, K23 CA148964-01)
  • Melanoma Research Alliance (1PO1 AI63302, 1R01 AI27655)
  • Viragh Foundation
  • Skip Viragh Pancreatic Cancer Center at Johns Hopkins
  • National Cancer Institute Specialized Programs of Research Excellence (SPORE)
  • Aduro Biotech Inc.
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
STING agonist, cancer vaccines, cyclic dinucleotides, anti-PD-1 resistance, PD-L1 upregulation, GM-CSF, dendritic cell activation, CD8+ T cells, type I interferon, cancer immunotherapy, tumor-infiltrating lymphocytes
MeSH terms
STING Protein, Animals, Antineoplastic Agents, Cytosol, Dendritic Cells, Female, Humans, Interferon-gamma, Ligands, Membrane Proteins, Mice, Inbred BALB C, Mice, Inbred C3H, Mice, Inbred C57BL, Monocytes, Neoplasm Transplantation, Phosphates, NF-kappa B, Protein Serine-Threonine Kinases, CD8-Positive T-Lymphocytes, Cancer Vaccines, Cell Line, Tumor, STAT6 Transcription Factor, Mice, Programmed Cell Death 1 Receptor

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