Therapeutic targeting of macrophages enhances chemotherapy efficacy by unleashing type I interferon response

Salvagno, C. et al. (2019) Therapeutic targeting of macrophages enhances chemotherapy efficacy by unleashing type I interferon response. Nature Cell Biology, 21(4), pp. 511-521. (doi:10.1038/s41556-019-0298-1) (PMID:30886344)

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Abstract

Recent studies have revealed a role for macrophages and neutrophils in limiting chemotherapy efficacy; however, the mechanisms underlying the therapeutic benefit of myeloid-targeting agents in combination with chemotherapy are incompletely understood. Here, we show that targeting tumour-associated macrophages by colony-stimulating factor-1 receptor (CSF-1R) blockade in the K14cre;Cdh1F/F;Trp53F/F transgenic mouse model for breast cancer stimulates intratumoural type I interferon (IFN) signalling, which enhances the anticancer efficacy of platinum-based chemotherapeutics. Notably, anti-CSF-1R treatment also increased intratumoural expression of type I IFN-stimulated genes in patients with cancer, confirming that CSF-1R blockade is a powerful strategy to trigger an intratumoural type I IFN response. By inducing an inflamed, type I IFN-enriched tumour microenvironment and by further targeting immunosuppressive neutrophils during cisplatin therapy, antitumour immunity was activated in this poorly immunogenic breast cancer mouse model. These data illustrate the importance of breaching multiple layers of immunosuppression during cytotoxic therapy to successfully engage antitumour immunity in breast cancer.

Item Type:Articles
Additional Information:This work was supported by the European Union (FP7 MCA-ITN 317445 TIMCC), the Dutch Cancer Society (NKI10623), the European Research Council (ERC consolidator award INFLAMET 615300), Worldwide Cancer Research (AICR 11-0677), the Netherlands Organization for Scientific Research NWO VIDI (917.96.307) and Oncode. K. Kos is supported by an OOA/NWO Diamond grant. K.E.d.V. is an EMBO Young Investigator. J.L.S. is a member of the Excellence Cluster ImmunoSensation and is in part supported by the DFG (SFB704, Excellence Cluster ImmunoSensation).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Coffelt, Dr Seth
Authors: Salvagno, C., Ciampricotti, M., Tuit, S., Hau, C.-S., van Weverwijk, A., Coffelt, S. B., Kersten, K., Vrijland, K., Kos, K., Ulas, T., Song, J.-Y., Ooi, C.-H., Rüttinger, D., Cassier, P. A., Jonkers, J., Schultze, J. L., Ries, C. H., and de Visser, K. E.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Nature Cell Biology
Publisher:Nature Research
ISSN:1465-7392
ISSN (Online):1476-4679
Published Online:18 March 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Nature Cell Biology 21(4): 511-521
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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