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The clinical and molecular significance associated with STING signaling in estrogen receptor-positive early breast cancer
Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2020.07.23.217398v1?rss=1
Authors: Parkes, E. E., Humphries, M. P., Gilmore, E., Sidi, F. A., Bingham, V., Phyu, S. M., Craig, S. G., Graham, C., Miller, J., Griffin, D., Kennedy, R. D., Bakhoum, S. F., McQuaid, S., Salto-Tellez, M., Buckley, N. E.
Abstract:
STING signaling in cancer is a crucial component of response to immunotherapy and other anti-cancer treatments. Conversely, STING signaling can promote tumor invasion and metastasis. 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, we identify perinuclear-localized expression of STING (pnSTING) in estrogen receptor-positive (ER+) breast cancer 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'-polarised macrophages. In ER- disease, pnSTING does not have a significant prognostic role, and STING appears to be uncoupled from interferon responses. Importantly, a gene signature defining low pnSTING expression in ER+ disease is predictive of poor prognosis in independent datasets. Low pnSTING is associated with chromosomal instability, MYC amplification and mTOR signaling, suggesting novel therapeutic approaches for this subgroup.
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Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2020.07.23.217398v1?rss=1
Authors: Parkes, E. E., Humphries, M. P., Gilmore, E., Sidi, F. A., Bingham, V., Phyu, S. M., Craig, S. G., Graham, C., Miller, J., Griffin, D., Kennedy, R. D., Bakhoum, S. F., McQuaid, S., Salto-Tellez, M., Buckley, N. E.
Abstract:
STING signaling in cancer is a crucial component of response to immunotherapy and other anti-cancer treatments. Conversely, STING signaling can promote tumor invasion and metastasis. 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, we identify perinuclear-localized expression of STING (pnSTING) in estrogen receptor-positive (ER+) breast cancer 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'-polarised macrophages. In ER- disease, pnSTING does not have a significant prognostic role, and STING appears to be uncoupled from interferon responses. Importantly, a gene signature defining low pnSTING expression in ER+ disease is predictive of poor prognosis in independent datasets. Low pnSTING is associated with chromosomal instability, MYC amplification and mTOR signaling, suggesting novel therapeutic approaches for this subgroup.
Copy rights belong to original authors. Visit the link for more info