IL-6 and IL-10 are associated with good prognosis in early stage invasive breast cancer patients

Ahmad, N., Ammar, A. , Storr, S., Green, A., Rakha, E., Ellis, I. and Martin, S. (2018) IL-6 and IL-10 are associated with good prognosis in early stage invasive breast cancer patients. Cancer Immunology, Immunotherapy, 67(4), pp. 537-549. (doi: 10.1007/s00262-017-2106-8) (PMID:29256156) (PMCID:PMC5860102)

Abstract

Macrophage-associated cytokines play an important role in cancer metastasis; however, the functions of interleukins (IL) 6 and 10 in breast cancer (BC) progression and metastasis are not clear. In this study the roles of IL-6/IL-10 in regulating vascular invasion and their prognostic significance in BC are investigated. MDA-MB-231 and MCF-7 migration (± IL-6 or IL-10) was assessed by scratch wound assay. Cancer cell adhesion to IL-6/IL-10 stimulated blood and lymphatic endothelial cells (EC) was investigated. Expression of IL-6 /IL-10 was assessed using immunohistochemistry in an annotated cohort of early stage BC (n = 1380) and associations with clinicopathological variables and clinical outcome evaluated. IL-6 did not alter BC cell migration however a dose-dependent inhibition in MDA-MB-231 migration with IL-10 treatment was observed (P = 0.03). BC cells were more adhesive to blood vs lymphatic EC, however, IL-6/IL-10 had no effect on adhesion patterns. High expression of IL-6/IL-10 was associated with clinicopathological criteria (e.g. hormone receptor status, all P < 0.05), improved disease-free survival (DFS; P < 0.05) and improved BC-specific survival (BCSS; only IL-6, P = 0.017). However, neither IL-6 nor IL-10 expression were independent prognostic factors from multivariate analysis. In BC subgroups, IL-6 and IL-10 were good prognosticators in terms of DFS in non-basal, non-triple-negative (non-TN), ER-positive, PgR-positive (only IL-10), and Her-2-negative (only IL-6) BC (all P < 0.05). IL-6 was associated with improved BCSS in non-basal, ER-positive and non-TN BC (all P < 0.05).

• Item Type: Articles
• Additional Information: The authors would like to acknowledge Breast Cancer Now for supporting this project (Grant Reference 2011NovSP025) and Sarah Storr (Grant Reference 2011MayPr35). Aula Ammar received funding from the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA Grant Agreement No. PCOFUND-GA-2012-600181.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Ammar, Dr Aula
• Authors: Ahmad, N., Ammar, A., Storr, S., Green, A., Rakha, E., Ellis, I., and Martin, S.
• Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Cancer Immunology, Immunotherapy
• Publisher: Springer
• ISSN: 0340-7004
• ISSN (Online): 1432-0851
• Published Online: 18 December 2017
• Copyright Holders: Copyright © 2017 The Authors
• First Published: First published in Cancer Immunology, Immunotherapy 67(4): 537-549
• Publisher Policy: Reproduced under a Creative Commons License