The clinical and molecular significance associated with STING signaling in breast cancer Journal Article
| Authors: | Parkes, E. E.; Humphries, M. P.; Gilmore, E.; Sidi, F. A.; Bingham, V.; Phyu, S. M.; Craig, S.; Graham, C.; Miller, J.; Griffin, D.; Salto-Tellez, M.; Madden, S. F.; Kennedy, R. D.; Bakhoum, S. F.; McQuaid, S.; Buckley, N. E. |
| Article Title: | 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 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. © 2021, The Author(s). |
| Keywords: | immunohistochemistry; signal transduction; controlled study; human tissue; protein expression; gene mutation; human cell; major clinical study; overall survival; somatic mutation; histopathology; interferon; cancer growth; cancer staging; outcome assessment; follow up; protein function; quality control; phenotype; progression free survival; breast cancer; gene amplification; gene expression; image analysis; cell infiltration; cohort analysis; genetic association; immunofluorescence; immune response; genetic transfection; immunotherapy; tumor cell; chromosomal instability; upregulation; tissue microarray; estrogen receptor; macrophage; mtor signaling; immunocompetent cell; oncogene myc; predictive value; recurrence free survival; wnt signaling; data extraction; cancer prognosis; human; female; article; immune checkpoint protein; experimental immunosuppression; immune cell infiltration; m2 macrophage; stimulator of interferon genes signaling |
| Journal Title: | npj Breast Cancer |
| Volume: | 7 |
| ISSN: | 2374-4677 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2021-06-25 |
| Start Page: | 81 |
| Language: | English |
| DOI: | 10.1038/s41523-021-00283-z |
| PROVIDER: | scopus |
| PMCID: | PMC8233333 |
| PUBMED: | 34172750 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 October 2021 -- Source: Scopus |
