npj Breast Cancer (Jun 2021)

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 F. Madden,
  • Richard D. Kennedy,
  • Samuel F. Bakhoum,
  • Stephen McQuaid,
  • Niamh E. Buckley

DOI
https://doi.org/10.1038/s41523-021-00283-z
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 11

Abstract

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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.