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Cited by 95interferon and immune responsesCancer Immunotherapy and BiomarkersImmunotherapy and Immune Responses

STING Signaling in Melanoma Cells Shapes Antigenicity and Can Promote Antitumor T-cell Activity

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Falahat, Rana, Perez-Villarroel, Patricio, Mailloux, Adam W., Zhu, Genyuan, Pilon-Thomas, Shari, Barber, Glen N., Mulé, James J.·2019·Cancer Immunology Research
DOI 10.1158/2326-6066.cir-19-0229PMC PMC6825582

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Abstract

STING (stimulator of IFN genes) signaling is an innate immune pathway for induction of a spontaneous antitumor T-cell response against certain immunogenic tumors. Although antigen-presenting cells are known to be involved in this process, insight into the participation of tumor cell–intrinsic STING signaling remains weak. In this study, we find diversity in the regulation of STING signaling across a panel of human melanoma cell lines. We show that intact activation of STING signaling in a subset of human melanoma cell lines enhances both their antigenicity and susceptibility to lysis by human melanoma tumor-infiltrating lymphocytes (TIL) through the augmentation of MHC class I expression. Conversely, defects in the STING signaling pathway protect melanoma cells from increased immune recognition by TILs and limit their sensitivity to TIL lysis. Based on these findings, we propose that defects in tumor cell–intrinsic STING signaling can mediate not only tumor immune evasion but also resistance to TIL-based immunotherapies.

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  • Activation of STING signaling in melanoma cells induces CXCL10 and CCL5.

    “Another aspect of the activation of STING signaling in melanoma cells is the downstream induction of CXCL10 and CCL529.”

    From Epigenetic state determines the in vivo efficacy of STING agonist therapy (2023) · cites this paper as [29]

    The Discussion (page unavailable) reports that STING activation by 2′3′-cGAMP induced CXCL10 in a subset of human melanoma cell lines. The Results section on intact STING signaling also reports CXCL10 induction, but our copy does not report induction of CCL5; searches for CCL5 and RANTES found no supporting passage. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • STING-dependent MHC class I upregulation in human and mouse melanoma cells following demethylation-mediated restoration of STING signaling can enhance both their antigenicity and susceptibility to lysis by CD8+ T cells.

    “This finding also coincides with our observation of STING-dependent MHC class I upregulation in human and mouse melanoma cells following demethylation-mediated restoration of STING signaling which can enhance both their antigenicity and susceptibility to lysis by CD8+ T cells29,37.”

    From Epigenetic state determines the in vivo efficacy of STING agonist therapy (2023) · cites this paper as [29]

    The Results report that STING agonist treatment increased MHC class I expression in human melanoma cell lines, and the Introduction reports enhanced recognition and lysis by human tumor-infiltrating lymphocytes. This paper does not report the same finding in mouse melanoma cells or following demethylation-mediated restoration of STING signaling. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Activation of STING signaling in human melanoma cell lines can increase their antigenicity by upregulating MHC class I molecules, leading to more effective immune recognition and antigen presentation to tumor-infiltrating lymphocytes.

    “we previously reported that activation of STING signaling in human melanoma cell lines can increase their antigenicity by upregulating MHC class I molecules, leading to more effective immune recognition and antigen presentation to tumor-infiltrating lymphocytes (TIL)29.”

    From Epigenetic state determines the in vivo efficacy of STING agonist therapy (2023) · cites this paper as [29]

  • In human melanoma cell lines, STING-mediated IFN-β induction can augment surface expression of MHC class I and render them better targets for cytotoxic CD8+ T cell recognition and killing.

    “Indeed, we have previously shown that in human melanoma cell lines STING-mediated IFN-β induction can augment their surface expression of MHC class I and therefore render them better targets for cytotoxic CD8+ T cell recognition and killing29,37.”

    From Epigenetic state determines the in vivo efficacy of STING agonist therapy (2023) · cites this paper as [29]

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Authors
Falahat, R., Perez-Villarroel, P., Mailloux, A. W., Zhu, G., Pilon-Thomas, S., Barber, G. N., & Mulé, J. J.
Affiliations
  • Moffitt Cancer Center (US)
  • 1Immunology Program, Moffitt Cancer Center, Tampa, Florida.
  • University of Miami (US)
Corresponding author
Mulé, James J.
ORCID
Venue
Cancer Immunology Research
Publisher
American Association for Cancer Research (AACR)
Published
2019-11-01
Volume
7
Issue
11
Pages
1837-1848
ISSN
  • 2326-6066 (ISSN-L)
  • 2326-6074
DOI
10.1158/2326-6066.cir-19-0229
PMC
PMC6825582
OpenAlex
W2970843395
Cited by
95
References
10
Citations by year
2026: 10 · 2025: 24 · 2024: 18 · 2023: 11 · 2022: 8 · 2021: 17 · 2020: 7
FWCI
3.20
Type
journal article
Language
en
Open access
Locations
  • Cancer Immunology Research (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • NCI-designated Comprehensive Cancer Center (P30-CA076292)
  • NCI NIH (1R01 CA148995, 1R01 CA184845, P30 CA076292, P50 CA168536)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
STING signaling, melanoma, tumor antigenicity, MHC class I expression, tumor-infiltrating lymphocytes, antitumor T-cell responses, tumor immune evasion, cancer cell lines
MeSH terms
STING Protein, Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase, Cytotoxicity, Immunologic, Humans, Melanoma, Membrane Proteins, Nucleotidyltransferases, Tumor Cells, Cultured, Histocompatibility Antigens Class I, Signal Transduction, Up-Regulation, Lymphocytes, Tumor-Infiltrating, Tumor Escape

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