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 with a significant drop between the earliest form of breast cancer, ductal carcinoma in situ (DCIS), and 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. Thus, her results will aid the clinical management of breast cancer by improving risk stratification and informing the design of more effective immunotherapies.

Progress Thus Far

Through their characterization of cellular and molecular alterations during breast tumor progression, Dr. Polyak and her team have observed a decline of 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. The immune cell repertoire (the variety of immune cells) in peripheral blood decreases naturally with age, 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 be a predictor of risk of breast cancer, age at diagnosis, and risk of progressive disease.

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. 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. Additionally, her studies have the potential to identify biomarkers to predict risk of progression and personalize treatments.

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