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

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journal contribution
posted on 2023-01-06, 17:36 authored by 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 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.

Publication Date

25 June 2021

PubMed ID

34172750

Department/Unit

  • Data Science Centre

Research Area

  • Cancer
  • Neurological and Psychiatric Disorders
  • Gynaecology, Obstetrics and Perinatal Health

Publisher

Nature Publishing Group

Version

  • Published Version (Version of Record)