Kornelia Polyak, MD, PhD

Understanding the role of the tumor immune microenvironment in pregnancy-associated breast cancer.

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 the recent increase in breast cancer diagnoses in women under 50, particularly post-partum breast cancer, Dr. Polyak is focused on understanding the potential contributors to this rising risk and specifically how immune cells are involved. The mammary gland is unique when it comes to the immune system, because most of its development occurs after birth—during puberty, pregnancy, and breastfeeding. Dr. Polyak’s research has shown that during different pregnancy stages a well-coordinated reshaping of immune cells around the breast occurs. She and her team are seeking to better understand the process by which this happens. Their work may inform strategies to prevent pro-cancer changes in immune cells as well as help create more effective immunotherapies.

Progress Thus Far

Previously, Dr. Polyak and her team found that T-cells, a type of immune cell, seem to play key roles in establishing an immunosuppressive environment in invasive tumors. Further analysis revealed distinct patterns in the types of T-cells in normal tissues compared to tumor-associated T-cells. Specifically, they found that T regulatory (Treg) cells, a naturally immune-suppressive cell were significantly more abundant in invasive breast cancer and blocking Tregs not only remodeled the tumor immune environment but also inhibited tumor growth. Through their characterization of changes in immune cells during breast tumor progression, Dr. Polyak and her team observed a decline in activated cancer killing immune cells called CD8+ T-cells. Further, the team found a link between mammary glands at various stages of pregnancy and increased expansion and activation of Tregs and CD8+ T cells. In the last year, they established mammary gland laboratory models that recapitulate stages of pregnancy to investigate how pregnancy influences tumorigenesis through the remodeling of the immune system. Initial single-cell immune profiling of mammary tissue allowed them to create a map of immune system changes during pregnancy. Using these models, Dr. Polyak observed an early increase in immunosuppressive Tregs from early to mid-pregnancy, before a big surge in CD8+ T cells.

What’s next

Dr. Polyak and her colleagues will continue to assess how the immune repertoire is associated with breast cancer initiation and progression, including the role of pregnancy-associated changes in immunosuppressive T cells and other immune cells. These studies will reveal how pregnancy changes breast tumor development by reshaping the immune systems. Dr. Polyak hopes this work will increase our understanding of breast cancer risk levels to prevent breast cancer as well as inform strategies for developing more effective immunotherapies, especially for pregnancy-associated breast cancer.