E. Aubrey Thompson, PhD

Understanding how breast tumor cells and immune cells interact and how this affects response to treatment.

Impact

The immune environment within a tumor affects how the tumor responds to chemotherapy and/or targeted treatments. Moreover, the interactions between cancer cells and immune cells also serve as targets for immunotherapies, such as checkpoint inhibitors. Dr. Thompson’s BCRF research is focused on understanding the relationship between response to therapy and the numbers, types, locations, and activities of immune cells in patients with aggressive breast cancers. These studies will provide fundamental new insight in tumor cell-immune cell interaction in high-risk breast cancer subtypes, as well as identify novel biomarkers and potential new therapeutic targets.

Progress Thus Far

Dr. Thompson’s focus is on early-stage triple-negative breast cancer (TNBC). He and his team analyzed the relationship between the immune landscape of TNBC and clinical outcome using emerging spatial biology technology. With this technique, they can map the abundance of immune and other tumor-related proteins within tumor microenvironments. A major focus has been on PD-L1, an immune regulatory protein that is expressed at high levels (PD-L1 positive) in some breast cancers and blocks the immune system from fighting tumor cells. Dr. Thompson and his team found several key immune features that are associated with PD-L1 positivity and have begun to understand why immune cells are excluded from certain tumors, meaning that these tumors have high immune cell density in the outer invasive margin but low immune cell density in the core. Dr. Thompson’s analysis of early-stage TNBC has contributed to the design of a novel clinical trial that is designed to overcome the phenomenon of immune exclusion and the poor prognosis that is associated with TNBC.

What’s next

In the upcoming year, Dr. Thompson and his team will continue studying immune exclusion. The team will analyze about 600 TNBC patient tissue samples and analyze the “fingerprint” of the genes activated in each individual cell. Dr. Thompson’s initial analyses will focus on a more detailed understanding of the features that determine immune exclusion and therefore clinical outcome in early-stage TNBC. In parallel, this dataset will be used as part of the team’s efforts to generate a spatial atlas of PD-L1 positivity in early-stage TNBC. The team will then use the results of those analyzes to analyze early-stage TNBC samples treated with neoadjuvant pembrolizumab, a drug that targets and blocks PD-L1 and stimulates the immune system to attack cancer cells. Knowing which genes are activated could aid in developing biomarkers of response to treatment and new therapeutic strategies.