BACKGROUND
Tumor infiltrating lymphocytes have been shown to predict clinical outcome in
breast cancer (BCa) patients, leading to the application of several
antibody-based immunotherapies for the treatment of late stage BCa. The
specific immune cell subtypes within the breast tissue responsible for
predicting outcome, and their role in the early stages of breast cancer
initiation however, has not been addressed. Investigating this area will determine
whether currently available immunotherapies are applicable to BCa patients, and
may also identify new immunotherapeutic targets for BCa.
MATERIALS AND METHODS
Using the transgenic MMTV-neuT spontaneous model of HER2+ BCa, we assessed the timing of breast cancer progression from hyperplasia through to DCIS and metastatic disease. We developed a mammary specific immunophenotyping FACS panel and used this to assess the immune cell compartment present in the mammary gland during hyperplasia and DCIS.
RESULTS
Our immune profiling revealed an increase in the number of macrophages present
in MMTV-neuT mice throughout hyperplasia and DCIS compared to WT mice. These
changes are also evident prior to the histological appearance of hyperplasia. Furthermore,
dendritic cells are also increased in MMTV-neuT mice during DCIS. We are
currently treating these MMTV-neuT mice with anti-CSF-1R monoclonal antibody to
the deplete macrophages, and block the early stages of breast cancer
development. This will allow us to determine the role of macrophages in the
initiation and progression of BCa.
CONCLUSIONS
This research has identified macrophages and dendritic cells, as new potential
targets for the use of immune-based therapeutics to treat early stage HER2+
breast cancer.