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; James J Mulé

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

Journal article

Open access

Peer reviewed

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 immunology research, Vol.7(11), pp.1837-1848

11/2019

DOI: 10.1158/2326-6066.CIR-19-0229

PMCID: PMC6825582

PMID: 31462408

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https://doi.org/10.1158/2326-6066.CIR-19-0229View

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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.

Cytotoxicity, Immunologic

Histocompatibility Antigens Class I - metabolism

Humans

Lymphocytes, Tumor-Infiltrating - immunology

Lymphocytes, Tumor-Infiltrating - metabolism

Melanoma - immunology

Melanoma - metabolism

Membrane Proteins - agonists

Membrane Proteins - metabolism

Nucleotidyltransferases - metabolism

Signal Transduction - immunology

Tumor Cells, Cultured

Tumor Escape - immunology

Up-Regulation

Details

Title: Subtitle: STING Signaling in Melanoma Cells Shapes Antigenicity and Can Promote Antitumor T-cell Activity
Creators: Rana Falahat - Moffitt Cancer Center
Patricio Perez-Villarroel - Moffitt Cancer Center
Adam W Mailloux - Moffitt Cancer Center
Genyuan Zhu - Moffitt Cancer Center
Shari Pilon-Thomas - Moffitt Cancer Center
Glen N Barber - University of Miami
James J Mulé - Moffitt Cancer Center
Resource Type: Journal article
Publication Details: Cancer immunology research, Vol.7(11), pp.1837-1848
DOI: 10.1158/2326-6066.CIR-19-0229
PMID: 31462408
PMCID: PMC6825582
NLM abbreviation: Cancer Immunol Res
ISSN: 2326-6066
eISSN: 2326-6074
Grant note: P50 CA168536 / NCI NIH HHS R01 CA184845 / NCI NIH HHS P30 CA076292 / NCI NIH HHS R01 CA148995 / NCI NIH HHS
Language: English
Date published: 11/2019
Academic Unit: Microbiology and Immunology
Record Identifier: 9984297425902771

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