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Cited by 487interferon and immune responsesImmunotherapy and Immune ResponsesCancer Immunotherapy and Biomarkers

The host STING pathway at the interface of cancer and immunity

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Corrales, Leticia, McWhirter, Sarah M., Dubensky, Thomas W., Gajewski, Thomas F.·2016·Journal of Clinical Investigation
DOI 10.1172/jci86892PMC PMC4922692
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Abstract

A major subset of human cancers shows evidence for spontaneous adaptive immunity, which is reflected by the presence of infiltrating CD8+ T cells specific for tumor antigens within the tumor microenvironment. This observation has raised the question of which innate immune sensing pathway might detect the presence of cancer and lead to a natural adaptive antitumor immune response in the absence of exogenous infectious pathogens. Evidence for a critical functional role for type I IFNs led to interrogation of candidate innate immune sensing pathways that might be triggered by tumor presence and induce type I IFN production. Such analyses have revealed a major role for the stimulator of IFN genes pathway (STING pathway), which senses cytosolic tumor-derived DNA within the cytosol of tumor-infiltrating DCs. Activation of this pathway is correlated with IFN-β production and induction of antitumor T cells. Based on the biology of this natural immune response, pharmacologic agonists of the STING pathway are being developed to augment and optimize STING activation as a cancer therapy. Intratumoral administration of STING agonists results in remarkable therapeutic activity in mouse models, and STING agonists are being carried forward into phase I clinical testing.

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  • CD8+IFN-γ+ T cells are an effector population shown to be a target of downstream STING signaling involving the IFN-β-CXCL9/10 axis.

    “an effector population shown to be a target of downstream STING signaling involving the IFN-β-CXCL9/10 axis.54–58”

    From Functional tumor cell-intrinsic STING, not host STING, drives local and systemic antitumor immunity and therapy efficacy following cryoablation (2023) · cites this paper as [54]

    The sections “Regulation of the STING pathway in APCs and its role in cancer” and “Type I IFNs in the generation of antitumor immune responses” link STING activation to IFN-β production and antitumor CD8+ T-cell responses. The latter section also associates CXCL9 and CXCL10 with T-cell recruitment, but our copy does not establish the stated IFN-β–CXCL9/10 signaling axis or identify CD8+IFN-γ+ T cells specifically as its target. (LLM, conf=0.85)

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Cited by

Sorted by citations

Authors
Corrales, L., McWhirter, S. M., Dubensky, T. W., & Gajewski, T. F.
Affiliations
  • University of Chicago (US)
  • Aduro BioTech (United States) (US)
Corresponding author
Gajewski, Thomas F.
ORCID
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
2016-07-01
Volume
126
Issue
7
Pages
2404-2411
ISSN
  • 0021-9738 (ISSN-L)
  • 1558-8238
DOI
10.1172/jci86892
PMC
PMC4922692
OpenAlex
W2466965232
Cited by
487
References
11
Citations by year
2026: 34 · 2025: 54 · 2024: 49 · 2023: 53 · 2022: 68 · 2021: 48 · 2020: 45 · 2019: 57 · 2018: 41 · 2017: 31 · 2016: 7
FWCI
4.37
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Cancer Research Institute
  • University of Chicago
  • National Cancer Institute (R01CA181160)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords
STING pathway, STING, innate immune recognition, type I interferon, interferon-beta, tumor-infiltrating dendritic cells, tumor-infiltrating CD8+ T cells, antitumor immunity, STING agonist, cancer immunotherapy, cytosolic DNA sensing, tumor microenvironment
MeSH terms
Animals, Antigen-Presenting Cells, Antineoplastic Agents, Cytosol, Dendritic Cells, DNA, Neoplasm, Humans, Immunity, Innate, Interferons, Neoplasms, Interferon-beta, CD8-Positive T-Lymphocytes, Mice, Adaptive Immunity, Tumor Microenvironment

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