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Cancer Immunology Research
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Research Articles

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

Rana Falahat, Patricio Perez-Villarroel, Adam W. Mailloux, Genyuan Zhu, Shari Pilon-Thomas, Glen N. Barber and James J. Mulé
Rana Falahat
1Immunology Program, Moffitt Cancer Center, Tampa, Florida.
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Patricio Perez-Villarroel
1Immunology Program, Moffitt Cancer Center, Tampa, Florida.
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Adam W. Mailloux
1Immunology Program, Moffitt Cancer Center, Tampa, Florida.
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Genyuan Zhu
1Immunology Program, Moffitt Cancer Center, Tampa, Florida.
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Shari Pilon-Thomas
1Immunology Program, Moffitt Cancer Center, Tampa, Florida.
2Cutaneous Oncology Program, Moffitt Cancer Center, Tampa, Florida.
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Glen N. Barber
3Department of Cell Biology, University of Miami Miller School of Medicine, Miami, Florida.
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James J. Mulé
1Immunology Program, Moffitt Cancer Center, Tampa, Florida.
2Cutaneous Oncology Program, Moffitt Cancer Center, Tampa, Florida.
4Radiation Oncology Department, Moffitt Cancer Center, Tampa, Florida.
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  • ORCID record for James J. Mulé
  • For correspondence: James.Mule@moffitt.org
DOI: 10.1158/2326-6066.CIR-19-0229 Published November 2019
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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.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Immunology Research Online (http://cancerimmunolres.aacrjournals.org/).

  • Cancer Immunol Res 2019;7:1837–48

  • Received March 28, 2019.
  • Revision received June 24, 2019.
  • Accepted August 22, 2019.
  • Published first August 28, 2019.
  • ©2019 American Association for Cancer Research.
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Cancer Immunology Research: 7 (11)
November 2019
Volume 7, Issue 11
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STING Signaling in Melanoma Cells Shapes Antigenicity and Can Promote Antitumor T-cell Activity
Rana Falahat, Patricio Perez-Villarroel, Adam W. Mailloux, Genyuan Zhu, Shari Pilon-Thomas, Glen N. Barber and James J. Mulé
Cancer Immunol Res November 1 2019 (7) (11) 1837-1848; DOI: 10.1158/2326-6066.CIR-19-0229

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STING Signaling in Melanoma Cells Shapes Antigenicity and Can Promote Antitumor T-cell Activity
Rana Falahat, Patricio Perez-Villarroel, Adam W. Mailloux, Genyuan Zhu, Shari Pilon-Thomas, Glen N. Barber and James J. Mulé
Cancer Immunol Res November 1 2019 (7) (11) 1837-1848; DOI: 10.1158/2326-6066.CIR-19-0229
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