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

Journal article

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

Authors: Parkes, EE; Humphries, MP; Gilmore, E; Sidi, FA; Bingham, V

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Research
• Journal: npj Breast Cancer
• Volume: 7
• Issue: 1
• Pages: 81-81
• Article number: 81
• Publication date: 2021-06-25
• DOI: 10.1038/s41523-021-00283-z
• EISSN: 2374-4677
• ISSN: 2374-4677
• Language: English
• Keywords: Immunohistochemistry; Cancer; Internal medicine; Breast cancer; Gene; Biology; Immunology; Downregulation and upregulation; Infiltration (HVAC); Cancer research; Immune system; Stimulator of interferon genes; Estrogen receptor; Signal transduction; Sting; Innate immune system; Immunotherapy; Medicine; Oncology