75P - Chemokine expression drives immune cell infiltration in response to oestrogen-deprivation in a model of oestrogen receptor positive breast cancer

Date 07 May 2015
Event IMPAKT 2015
Session Welcome reception and Poster Walk
Topics Basic Science
Breast Cancer
Cancer Immunology and Immunotherapy
Presenter Anita Dunbier
Citation Annals of Oncology (2015) 26 (suppl_3): 25-26. 10.1093/annonc/mdv118
Authors A. Dunbier, J. Hazlett, B. Hunter, R. Kemp
  • Centre For Translational Cancer Research, University of Otago, 9016 - Dunedin/NZ



Background: Previous analysis has revealed that high pre-treatment expression of an inflammatory gene expression signature and lymphocytic infiltration are correlated with poor response to neoadjuvant aromatase inhibitor treatment. In addition, inflammatory gene expression has been found to increase upon treatment with AIs. These observations differ from that seen in tumours treated with neoadjuvant chemotherapy and analyses of HER2 + ve patients.

Aims: This study set out to investigate the mechanisms that drive immune cell infiltration during anti-oestrogen therapy in ER + ve breast cancer. Methods: Expression of key chemokines was analysed by QPCR and BioPlex analysis in oestrogen-deprived MCF-7 cells. A model of immune cell migration was generated by placing purified peripheral blood mononuclear cells (PBMCs) in transwell chambers above cultured MCF7 cells and measuring the level of migration towards the tumour cells. Flow cytometry analysis was carried out on the migrated cells. Chemokine blocking proteins were added to assess their ability to block migration.

Results: Analysis of oestrogen-deprived MCF7 cells revealed that oestrogen deprivation induced expression of chemokines including CCL5, CXCL16, and CCL22. This was confirmed by Bioplex analysis and these genes also increased in response to treatment with aromatase inhibitors in ER + ve breast cancers. In addition, a significant increase in the total number of PBMCs migrating to oestrogen deprived cells compared to cells with normal levels of E2 (p < 0.0001) was observed. Furthermore, FACS analysis revealed a significant increase in the number of CD4+ cells and a decrease in the number of CD11+ cells migrating to deprived cells (p < 0.05). This migration was blocked by addition of a broad specificity chemokine-binding protein and to a lesser degree by a CCL5-specific protein.

Conclusions: These data suggest that oestrogen deprivation-induced chemokine production induces recruitment of immune cells towards ER + ve breast cancer cells and this response may contribute to resistance to anti-oestrogen therapy. Targeting this inflammatory response could be a future direction for therapy.

Disclosure: All authors have declared no conflicts of interest.