期刊
NPJ BREAST CANCER
卷 7, 期 1, 页码 -出版社
NATURE RESEARCH
DOI: 10.1038/s41523-021-00283-z
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资金
- Northern Ireland Biobank
- HSC Research and Development Division of the Public Health Agency in Northern Ireland
- Friends of the Cancer Centre
- Academy of Medical Sciences
- Prostate Cancer Foundation
- Oxford Institute for Radiation Oncology
- CRUK Accelerator [C11512/A20256]
- NVIDIA Corporation via the GPU Grant Program
- British Research Council
- Breast Cancer Now Scientific Fellowship [2012MaySF122]
The study introduces a new method to assess STING activation in tumor cells, showing that pnSTING expression is associated with good prognosis in ER+ breast cancer but not in ER- disease. Additionally, low pnSTING is linked to chromosomal instability, MYC amplification, and mTOR signaling.
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.
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