Kornelia Polyak, MD, PhD

Understanding the timing and underlying mechanism by which cancer cells escape the immune system to become invasive and metastatic.

Impact

The immune system is one of our body’s most effective defense mechanisms against cancer. The ability of immune cells to attack cancer cells is critical to prevent tumor initiation and progression. Unfortunately, cancer cells have developed methods to survive this immune attack, allowing tumors to grow, become invasive, and metastasize—this process is termed immune escape. Dr. Polyak and others have described a progressive decrease in active immune cells during disease progression particularly during the transition from ductal carcinoma in situ (DCIS), the earliest form of breast cancer, to invasive carcinoma (IDC). Dr. Polyak and her team have been analyzing the immune cells in normal breast tissue and breast tumors to assess when and how tumor cells escape immune surveillance during this progression. These investigations have the potential to identify markers to predict whether a DCIS is likely to progress to invasive disease, as well as which invasive tumors are likely to respond to immunotherapy.

Progress Thus Far

Through their characterization of cellular and molecular alterations during breast tumor progression, Dr. Polyak and her team have observed a decline in activated cancer killing immune cells (CD8+ T-cells) during the transition from DCIS to invasive breast cancer. Using laboratory models they developed, her team found that other immune cells prevented the progression of early-stage tumors and, in some cases, induced complete tumor regression. Recently, they found that there are fewer active immune cells in the blood samples of patients with IDC compared to those with DCIS, confirming what they saw in their laboratory experiments. Dr. Polyak’s research has shown that they are also lower in young women diagnosed with metastatic breast cancer compared to those diagnosed with DCIS. These results imply that pre-existing immune repertoire may provide some clues about breast cancer risk or risk of progressive disease. In the last year, her team compared the cellular and molecular composition of normal mammary glands versus mammary tumors in laboratory models. They identified an immune cell subpopulation, T-cells, that seems to play key roles in establishing the immunosuppressive environment in invasive tumors.

What’s next

Dr. Polyak and her colleagues will continue to assess the changes in myoepithelial cells between normal, DCIS, and IDC cells. Ongoing analysis of this data may reveal the process of immune escape that occurs in the DCIS to ICDC transition. Using their previously developed laboratory models, they will continue to assess how the immune repertoire is associated with breast cancer initiation and progression, including the role of immunosuppressive T cells in breast cancer progression. Dr. Polyak hopes to gain a better understanding of how breast tumors evade the immune system so that more effective immunotherapies can be developed to treat both early and advanced stage disease.