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Title of Journal: Breast Cancer Res Treat

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Abbravation: Breast Cancer Research and Treatment

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Publisher

Springer US

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ISSN

1573-7217

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Characterisation of tumourinfiltrating macrophage

Authors: Steven D Heys Keith N Stewart Emma J McKenzie Iain D Miller Simon Y C Wong Grant Sellar Andrew J Rees
Publish Date: 2012/08/11
Volume: 135, Issue: 2, Pages: 539-548
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Abstract

The role of the tumour microenvironment and complex cellular interactions has attracted interest in responses to primary chemotherapy Of particular interest are tumourinfiltrating T cells and tumourinfiltrating macrophages TIMs We evaluated TIMs and their key activation markers in patients with breast cancer undergoing primary chemotherapy related to response and survival One hundred and ninety nine patients with large or locally advanced breast cancers received primary chemotherapy Clinical data histopathological responses to chemotherapy and survival were examined related to infiltrating cells in tumour microenvironments cluster of differentiation CD3 pan T cell CD4 helper T cells CD8 cytotoxic T cells CD25 activated T cells CD68 suppressor of cytokine signalling SOCS1 SOCS3 macrophages and CD11c and CD205 dendritic In tumours demonstrating better responses to chemotherapy there were significantly fewer CD4+ Thelper cells than a poorer response p  005 There were increased numbers of SOCS3 expressing macrophages proinflammatory in tumours with complete pathological responses compared with no response to chemotherapy p  005 There was no association between SOCS1 expressing macrophages antiinflammatory and tumour response Multivariate analysis revealed that factors indicating better survival were receiving anthracycline plus docetaxel ExpB = 1166 p = 0006 better pathological chemotherapy response ExpB = 0309 p = 0009 and a low macrophage SOCS1 expression ExpB = 13465 p = 0044 This study highlights the heterogeneity of TIMs and provides further insight into complex interactions within tumours The results emphasise the importance of characterising activation status of infiltrating macrophages and provides proof of principle for using macrophage SOCS protein expression as a survival predictor The apparent impact of macrophage subsets on overall survival underlines the therapeutic potential of manipulating macrophage activation in cancerThis work was supported by an award ONCAU061 from the Translational Medicine Research Collaboration—a consortium made up of the Universities of Aberdeen Dundee Edinburgh and Glasgow the four associated NHS Health Boards Grampian Tayside Lothian and Greater Glasgow and Clyde Scottish Enterprise and Pfizer formerly Wyeth Keith N Stewart and Emma J McKenzie contributed equally to this work

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