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

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

Online: https://www.nature.com/articles/s41523-021-00283-z

Issue: NPJ Breast Cancer. 2021 Jun 25;7(1):81.


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.