Decreased NK-cell tumour immunosurveillance consequent to JAK inhibition enhances metastasis in breast cancer models

Alessia Bottos, Dagmar Gotthardt, Jason W. Gill, Albana Gattelli, Anna Frei, Alexandar Tzankov, Veronika Sexl, Aleksandra Wodnar-Filipowicz () and Nancy E. Hynes ()
Additional contact information
Alessia Bottos: Friedrich Miescher Institute for Biomedical Research
Dagmar Gotthardt: Institute of Pharmacology and Toxicology, University of Veterinary Medicine
Jason W. Gill: Friedrich Miescher Institute for Biomedical Research
Albana Gattelli: Friedrich Miescher Institute for Biomedical Research
Anna Frei: Friedrich Miescher Institute for Biomedical Research
Alexandar Tzankov: Institute of Pathology, University Hospital Basel
Veronika Sexl: Institute of Pharmacology and Toxicology, University of Veterinary Medicine
Aleksandra Wodnar-Filipowicz: Stem Cell Center of Competence, University of Basel
Nancy E. Hynes: Friedrich Miescher Institute for Biomedical Research

Nature Communications, 2016, vol. 7, issue 1, 1-12

Abstract: Abstract The JAK/STAT pathway is an attractive target for breast cancer therapy due to its frequent activation, and clinical trials evaluating JAK inhibitors (JAKi) in advanced breast cancer are ongoing. Using patient biopsies and preclinical models of breast cancer, we demonstrate that the JAK/STAT pathway is active in metastasis. Unexpectedly, blocking the pathway with JAKi enhances the metastatic burden in experimental and orthotopic models of breast cancer metastasis. We demonstrate that this prometastatic effect is due to the immunosuppressive activity of JAKi with ensuing impairment of NK-cell-mediated anti-tumour immunity. Furthermore, we show that immunostimulation with IL-15 overcomes the enhancing effect of JAKi on metastasis formation. Our findings highlight the importance of evaluating the effect of targeted therapy on the tumour environment. The impact of JAKi on NK cells and the potential value of immunostimulators to overcome the weakened tumour immunosurveillance, are worthwhile considering in the clinical setting of breast cancer.

Date: 2016
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms12258 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12258

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms12258

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().