posted on 2023-01-06, 17:36authored byEileen 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 MaddenStephen Madden, Richard D Kennedy, Samuel F Bakhoum, Stephen McQuaid, Niamh E Buckley
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.
Funding
HSC Research and Development Division of the Public Health Agency in Northern Ireland
Friends of the Cancer Centre
Academy of Medical Sciences (Starter Grant for Clinical Lecturers)
Prostate Cancer Foundation (Young Investigator Award)
Oxford Institute for Radiation Oncology
CRUK Accelerator (C11512/A20256)
NVIDIA Corporation via the GPU Grant Program for researchers
British Research Council
Breast Cancer Now Scientific Fellowship (2012MaySF122)
History
Comments
The original article is available at https://www.nature.com/
Published Citation
Parkes EE. et al. The clinical and molecular significance associated with STING signaling in breast cancer. NPJ Breast Cancer. 2021;7(1):81.