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

Bottos, Alessia and Gill, Jason W and Tzankov, Alexander and Wodnar-Filipowicz, Aleksandra and Hynes, Nancy E (2016) Decreased NK-cell tumour immunosurveillance consequent to JAK inhibition enhances metastasis in breast cancer models. Nature communications, 7 (12258). pp. 1-12. ISSN 2041-1723

Abstract

The JAK/STAT pathway is an attractive target in breast cancer therapy due to its frequent activation. Clinical trials evaluating the efficacy of JAK inhibitors (JAKi) in advanced breast cancer are ongoing, making it important to understand the effect of this therapeutic approach on metastasis. Using patient biopsies and preclinical models of breast cancer, we demonstrate that the JAK/STAT pathway is active in bone metastasis, in both the cancer cells and in the tumor environment. Unexpectedly, blocking the pathway with JAKi enhanced the metastatic burden in experimental and spontaneous models of breast cancer metastasis. We demonstrate that this pro-metastatic effect is due to the immunosuppressive activity of JAKi with ensuing impairment of NK cell-mediated anti-tumor immunity. These findings highlight the importance of evaluating the effect of targeted therapy on the tumor environment in addition to the cancer cells. Moreover, we suggest that the impact of JAKi on the immune system warrants clinical monitoring for potential harmful effects of JAK pathway inhibition in breast cancer patients.

Item Type: Article
Date Deposited: 12 Oct 2016 00:45
Last Modified: 12 Oct 2016 00:45
URI: https://oak.novartis.com/id/eprint/25306

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