Poster Presentation 27th Lorne Cancer Conference 2015

Assessing the immune profile of MMTV-HER2neu mice during hyperplasia to identify cells involved in promoting breast cancer development   (#290)

Ashleigh Unsworth 1 2 , Jessica Vieusseux 1 , Genevieve Dall 1 3 , Misty Jenkins 1 , Robin Anderson 1 , Nicole Haynes 1 , Kara Britt 1
  1. Sir Peter MacCallum Oncology Department, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia
  2. The University of Melbourne, Parkville, VIC, Australia
  3. Anatomy Department, Monash University, Clayton, VIC, Australia

The immune microenvironment has been shown to predict clinical outcome in breast cancer patients, leading to the development of effective antibody-based immunotherapies for the treatment of late stage breast cancer. However the role of the immune microenvironment in early breast cancer tumor cell surveillance and elimination is not well understood. Investigating this area may assist in identifying new targets for the development of chemopreventative drugs for women, particularly those at an increased risk of developing breast cancer. To explore this we are using the transgenic MMTV-HER2-neu spontaneous model of breast cancer, which exhibit atypical ductal hyperplasia by 9 weeks of age, DCIS by 11 weeks of age, and palpable tumors by 16-17 weeks of age. To identify changes that occur prior to tumor development, we are analyzing the immune cell compartment present in the mammary gland during 3 time points within the pre-neoplastic phase (4-5, 6-7 and 8-9 weeks of age) using flow cytometry and cytometric cytokine bead arrays. Our immune profiling revealed an increase in the number of myeloid cells (CD11b+) in MMTV-HER2-neu mice during pre-neoplasia compared to WT mice. This was due to a rise in the number of macrophages, neutrophils and dendritic cells in the myeloid population. We are investigating the cytokine signaling of these myeloid cells to help elucidate how these cells may be promoting tumorigenesis. This could help us identify targets for the development of pre-clinical therapeutic interventions aimed at improving tumor surveillance and delaying or inhibiting tumor onset.