IL-6 and IL-10 are associated with good prognosis in early stage invasive breast cancer patientsTools Ahmad, Narmeen, Ammar, Aula, Storr, Sarah J., Green, Andrew R., Rakha, Emad, Ellis, Ian and Martin, Stewart G. (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. ISSN 1432-0851
AbstractMacrophage-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).
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