Type I interferon/IRF7 axis instigates chemotherapy-induced immunological dormancy in breast cancer View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-04

AUTHORS

Qiang Lan, Sanam Peyvandi, Nathalie Duffey, Yu-Ting Huang, David Barras, Werner Held, François Richard, Mauro Delorenzi, Christos Sotiriou, Christine Desmedt, Girieca Lorusso, Curzio Rüegg

ABSTRACT

Neoadjuvant and adjuvant chemotherapies provide survival benefits to breast cancer patients, in particular in estrogen receptor negative (ER-) cancers, by reducing rates of recurrences. It is assumed that the benefits of (neo)adjuvant chemotherapy are due to the killing of disseminated, residual cancer cells, however, there is no formal evidence for it. Here, we provide experimental evidence that ER- breast cancer cells that survived high-dose Doxorubicin and Methotrexate based chemotherapies elicit a state of immunological dormancy. Hallmark of this dormant phenotype is the sustained activation of the IRF7/IFN-β/IFNAR axis subsisting beyond chemotherapy treatment. Upregulation of IRF7 in treated cancer cells promoted resistance to chemotherapy, reduced cell growth and induced switching of the response from a myeloid derived suppressor cell-dominated immune response to a CD4+/CD8+ T cell-dependent anti-tumor response. IRF7 silencing in tumor cells or systemic blocking of IFNAR reversed the state of dormancy, while spontaneous escape from dormancy was associated with loss of IFN-β production. Presence of IFN-β in the circulation of ER- breast cancer patients treated with neoadjuvant Epirubicin chemotherapy correlated with a significantly longer distant metastasis-free survival. These findings establish chemotherapy-induced immunological dormancy in ER- breast cancer as a novel concept for (neo)adjuvant chemotherapy activity, and implicate sustained activation of the IRF7/IFN-β/IFNAR pathway in this effect. Further, IFN-β emerges as a potential predictive biomarker and therapeutic molecule to improve outcome of ER- breast cancer patients treated with (neo)adjuvant chemotherapy. More... »

PAGES

1-16

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41388-018-0624-2

DOI

http://dx.doi.org/10.1038/s41388-018-0624-2

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1110584034

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30546090


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