Project 467238

The focus of this project is on a type of breast cancer called triple-negative breast cancer (TNBC) that is very aggressive and has a poor prognosis. It affects mainly young women in the prime of life, people of African ancestry, and people that carry the heritable breast cancer gene, BRCA1.We have recently discovered that TNBCs grow by releasing special proteins called cytokines. Cytokines act as beacons to attract immune cells to the tumor and against expectations, can help the tumor grow and spread.Cytokines are usually secreted by immune cells to attract disease-fighting cells to a site of disease. We found that TNBC cells mimic immune cells and have learned how to assemble the inflammasome, machinery required to secrete a cytokine called IL1?. Based on studies of the immune system, scientists have known for decades that abnormal cytokine secretion can promote inflammatory diseases like arthritis. Therefore, drugs that target the inflammasome and cytokines have been developed. Based on our work, drugs that prevent IL1? production may provide powerful immunotherapy to fight TNBC.The objective of this project will be to confirm which cytokines are released from breast cancers, and to determine which types of immune cells are attracted as a result. In this project, using mice that develop breast cancer, anti-IL1? drugs will be tested alone or in combination with other immunotherapies. This will help identify immunotherapies that may be effective in treating TNBC.This project will provide evidence that TNBC patients can be effectively treated with immunotherapies that target inflammatory diseases. Repurposing these drugs for cancer could rapidly reduce time and cost of current therapies and save the lives of patients who previously had few options.