The clinical and molecular significance associated with STING signaling in breast cancer.
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Embargo End Date
ICR Authors
Authors
Parkes, EE
Humphries, MP
Gilmore, E
Sidi, FA
Bingham, V
Phyu, SM
Craig, S
Graham, C
Miller, J
Griffin, D
Salto-Tellez, M
Madden, SF
Kennedy, RD
Bakhoum, SF
McQuaid, S
Buckley, NE
Humphries, MP
Gilmore, E
Sidi, FA
Bingham, V
Phyu, SM
Craig, S
Graham, C
Miller, J
Griffin, D
Salto-Tellez, M
Madden, SF
Kennedy, RD
Bakhoum, SF
McQuaid, S
Buckley, NE
Document Type
Journal Article
Date
2021-06-25
Date Accepted
2021-05-27
Abstract
STING signaling in cancer is a crucial component of response to immunotherapy and other anti-cancer treatments. Currently, there is no robust method of measuring STING activation in cancer. Here, we describe an immunohistochemistry-based assay with digital pathology assessment of STING in tumor cells. Using this novel approach in estrogen receptor-positive (ER+) and ER- breast cancer, we identify perinuclear-localized expression of STING (pnSTING) in ER+ cases as an independent predictor of good prognosis, associated with immune cell infiltration and upregulation of immune checkpoints. Tumors with low pnSTING are immunosuppressed with increased infiltration of "M2"-polarized macrophages. In ER- disease, pnSTING does not appear to have a significant prognostic role with STING uncoupled from interferon responses. Importantly, a gene signature defining low pnSTING expression is predictive of poor prognosis in independent ER+ datasets. Low pnSTING is associated with chromosomal instability, MYC amplification and mTOR signaling, suggesting novel therapeutic approaches for this subgroup.
Citation
NPJ breast cancer, 2021, 7 (1), pp. 81 - ?
Source Title
Publisher
NATURE PORTFOLIO
ISSN
2374-4677
eISSN
2374-4677
Collections
Research Team
Integrated Pathology
Integrated Pathology
Integrated Pathology