The clinical and molecular significance associated with STING signaling in breast cancer

Eileen E. Parkes, Matthew P. Humphries, Elaine Gilmore, Fatima A. Sidi, Victoria Bingham, Su M. Phyu, Stephanie Craig, Catherine Graham, Joseph Miller, Daryl Griffin, Manuel Salto-Tellez, Stephen Madden, Richard D. Kennedy, Samuel F Bakhoum, Stephen McQuaid, Niamh E Buckley*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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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.
Original languageEnglish
Article number81
Number of pages11
Journalnpj Breast Cancer
Volume7
DOIs
Publication statusPublished - 25 Jun 2021

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