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

Lead Research Organisation: University of Edinburgh
Department Name: MRC Centre for Reproductive Health

Abstract

Development of metastatic tumors dramatically reduces survival rate of breast cancer patients, thus suppression of metastatic tumor outgrowth is essential to prolong overall survival of patients. Metastatic breast cancer is primarily treated by cytotoxic agents such as Doxorubicin, but response to single treatment is restricted by resistance to the agent. An alternative strategy is immunotherapy utilizing cancer vaccines or immune-checkpoint inhibitors, although its application appears to be limited to tumors expressing specific antigens. Another option is adoptive transfer of NK cells, which is reported to be safe and have modest efficacy in metastatic breast cancer, whereas data suggest that NK cells cannot exhibit full cytotoxic capacity in the tumor microenvironment. Although resistance to these therapies can be caused by tumor cell intrinsic mechanisms, recent studies using primary tumor models suggest pivotal roles of tumor-associated macrophages (TAMs). Using metastatic breast cancer mouse models, we have reported that TAMs are recruited to the metastatic lung and interact with disseminating breast cancer cells via chemokine signals, which promotes metastatic tumor outgrowth.
The aim of this project is to test whether macrophage blockade by inhibiting these chemokine signals can improve efficacies of doxorubicin treatment and NK-cell-based immunotherapy.
 
Description Edinburgh Science Festival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Stall set up at science festival in Edinburgh to show what the Centre for reproductive health researchers. There were fetus' of different ages in small tubes and children had to put them in order of age. We had photos of lung sections where people could try to identify tumours. We had histological slides where the public could look through the microscope to see how different tissues looked.
Year(s) Of Engagement Activity 2019