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

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 t...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/6790f073307d4fffbb5fb02a2f06cc1f
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spelling	oai:doaj.org-article:6790f073307d4fffbb5fb02a2f06cc1f2021-12-02T18:02:38ZThe clinical and molecular significance associated with STING signaling in breast cancer10.1038/s41523-021-00283-z2374-4677https://doaj.org/article/6790f073307d4fffbb5fb02a2f06cc1f2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41523-021-00283-zhttps://doaj.org/toc/2374-4677Abstract 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.Eileen E. ParkesMatthew P. HumphriesElaine GilmoreFatima A. SidiVictoria BinghamSu M. PhyuStephanie CraigCatherine GrahamJoseph MillerDaryl GriffinManuel Salto-TellezStephen F. MaddenRichard D. KennedySamuel F. BakhoumStephen McQuaidNiamh E. BuckleyNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Breast Cancer, Vol 7, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 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 The clinical and molecular significance associated with STING signaling in breast cancer
description	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.
format	article
author	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
author_facet	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
author_sort	Eileen E. Parkes
title	The clinical and molecular significance associated with STING signaling in breast cancer
title_short	The clinical and molecular significance associated with STING signaling in breast cancer
title_full	The clinical and molecular significance associated with STING signaling in breast cancer
title_fullStr	The clinical and molecular significance associated with STING signaling in breast cancer
title_full_unstemmed	The clinical and molecular significance associated with STING signaling in breast cancer
title_sort	clinical and molecular significance associated with sting signaling in breast cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6790f073307d4fffbb5fb02a2f06cc1f
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The clinical and molecular significance associated with STING signaling in breast cancer

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