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Breast cancer immune microenvironment: from pre-clinical models to clinical therapies

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Abstract

The breast cancer tumour microenvironment (BC-TME) is characterized by significant cellular and spatial heterogeneity that has important clinical implications and can affect response to therapy. There is a growing need to develop methods that reliably quantify and characterize the BC-TME and model its composition and functions in experimental systems, in the hope of developing new treatments for patients. In this review, we examine the role of immune-activating cells (including tumour-infiltrating lymphocytes and natural killer cells) and immune inhibitory cells (including T regulatory cells, tumour-associated macrophages and myeloid-derived suppressor cells) in the BC-TME. We summarize methods being used to characterize the microenvironment, with specific attention to pre-clinical models including co-cultures, organoids, and genetically modified and humanized mouse models. Finally, we explore the implications and applications of existing preclinical data for drug development and highlight several drugs designed to alter the BC-TME in order to improve treatment outcomes for patients.

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Acknowledgements

Dr. Brooke E. Wilson was supported as a National Breast Cancer Foundation of Australia International Fellow. Dr. David W. Cescon is supported by the Canadian Institutes of Health Research, the Princess Margaret Cancer Foundation and the DH Gales Family Foundation.

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  1. Chiara Gorrini

    Present address: Paediatric Solid Tumour Biology and Therapeutics, The Institute of Cancer Research, London, UK

Authors and Affiliations

  1. Division of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre and the University of Toronto, 610 University Ave, 700U, 7-305W, Toronto, ON, M5G 2M9, Canada

    Brooke E. Wilson & David W. Cescon

  2. University of New South Wales, Kensington, NSW, Australia

    Brooke E. Wilson

  3. Princess Margaret Cancer Centre, University Health Network, Toronto, China

    Chiara Gorrini

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BW reports consulting fees from Maple Health Group, outside the submitted work. DWC reports consulting/advisory fees from Agendia, AstraZeneca, Dynamo Therapeutics, Eisai, Exact Sciences, Gilead, GlaxoSmithKline, Merck, Novartis, Pfizer, Puma Biotechnology, and Roche; research support (to institution) from GlaxoSmithKline, Inivata, Merck, Pfizer and Roche; and intellectual property including methods of treating cancers characterized by a high expression level of spindle and kinetochore-associated complex subunit 3 (ska3) gene (US62/675,228), all outside of the submitted work.

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Wilson, B.E., Gorrini, C. & Cescon, D.W. Breast cancer immune microenvironment: from pre-clinical models to clinical therapies. Breast Cancer Res Treat 191, 257–267 (2022). https://doi.org/10.1007/s10549-021-06431-0

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  • DOI: https://doi.org/10.1007/s10549-021-06431-0

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