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 ways to  escape immune attack, allowing tumors to grow, become invasive, and metastasize. 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 both for high-risk DCIS, those most 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. Building on these findings, Dr. Polyak is characterizing the role myoepithelial cells (those that line the milk ducts) play in preventing immune cell infiltration and interaction with cancer cells. To accomplish this, they are employing single cell analytics to delineate differences in myoepithelial cells in normal, DCIS, and IDC. Preliminary results indicate that there are significant gene expression changes in all cell types. 

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. Her team will also continue to examine how the immune status of the patient may influence the immune microenvironment of the tumor and the risk of tumor progression.