Role of macrophage chemokine signals in efficacy of therapeutic modalities for metastatic outgrowth of breast cancer cells

Year of award: 2015


  • Dr Takanori Kitamura

    University of Edinburgh

Project summary

Metastatic breast cancer cannot be cured using current therapies including chemotherapy and immunotherapy. However, studies suggest that the efficacy of these therapies can be improved by depletion of macrophages as these cells protect breast cancer cells from the effects of cytotoxic drugs, such as doxorubicin, and immune cells, such as NK cells. We found that macrophages are recruited to the metastatic lung and interact with disseminating breast cancer cells via chemokine signals, which promotes metastatic tumour outgrowth. We will test whether macrophage blockade by chemokine receptor inhibition improves the efficacy of doxorubicin and NK-cell-based immunotherapy.

We have prepared bone marrow chimeric mice that lack chemokine receptors and mouse breast cancer cells that are killed by doxorubicin or NK cells in vitro but not in the tumour’s microenvironment. Using these tools and chemokine receptor antagonists, we will test whether chemokine receptor inhibition affects metastatic tumour growth in lungs under doxorubicin treatment or adoptive transfer of NK cells. We will also investigate number and status of cytotoxic immune cells, vascular status, and tumour cell apoptosis using flow cytometry and immunostaining to address possible mechanisms.

This study will test whether inhibition of macrophage-mediated chemokine signals can be a new strategy to improve therapeutic modalities for metastatic breast cancer.