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Kornelia Polyak, MD, PhD
Professor of Medicine, Harvard Medical School
Principal Faculty, Harvard Stem Cell Institute
Dana-Farber Cancer Institute/Harvard Medical School
- Seeking to understand the role of the immune system in cancer development and growth.
- Laboratory studies are ongoing to characterize the properties of tumor infiltrating immune cells to understand their role in the transition from pre-malignant to invasive breast cancer.
- These studies are important to our understanding of tumor growth and may inform novel prevention and treatment strategies.
Breast cancer cells start out as normal breast cells, but over time, they evolve to look less like breast cells. They change shape to breakout of the normal tissue architecture and activate cellular programs that cause them to look different on the outside. As they evolve to look less normal, the immune system takes notice and cells called natural killer cells come in to kill the tumor cells. However, tumor cells can co-opt the immune cells for their purposes. Dr. Polyak is conducting studies to understand how this occurs in order to devise strategies to enhance anti-tumor immune response.
Full Research Summary
Over the course of her BCRF-supported research, Dr. Polyak has found that tumors are made up of a diverse collection of cancer cells with very different properties. Her work has also revealed that the greater this intra-tumor heterogeneity, the more likely that the tumor will be resistant to treatment and will progress to metastatic disease.
In her current work, Dr. Polyak is studying the role of immune cells in the tumor microenvironment on tumor progression from noninvasive to invasive disease.
Leukocytes (white blood cells) have both tumor suppressive and tumor promoting properties. Dr. Polyak's team found significant differences in the types of leukocytes that infiltrate pre-invasive and invasive breast tumors compared to those in normal breast tissues. Some of these leukocytes represent active immune responses against the tumor, but tumor cells can suppress this response.
Research from the Polyak lab has shown that immune response diminishes as tumors become invasive, supporting a rationale for assessing immune status to identify women at high risk of progression.
During the coming year, the team will study cellular and molecular changes in non-invasive ductal carcinoma in situ to understand how these events lead to immune evasion. They will also test strategies to activate the immune system to block breast tumor progression in laboratory models of breast cancer.
These studies will improve our understanding of how cancer cells and the immune cells cooperate during breast tumor progression and allow tumors to escape immune surveillance. This knowledge can guide the design of more effective immunotherapies for the elimination of both early and late stage breast cancers.
Kornelia Polyak, MD, PhD is a Professor of Medicine at Dana-Farber Cancer Institute, Harvard Medical School, and is an internationally recognized leader in the breast cancer field. Research in Dr. Polyak’s laboratory is dedicated to the molecular analysis of human breast cancer with the goal of identifying differences between normal and cancerous breast tissue, determining their consequences, and using this information to improve the clinical management of breast cancer patients. Her lab has devoted much effort to develop new ways to study tumors as a whole and to apply interdisciplinary approaches. Using these methods, Dr. Polyak’s lab been at the forefront of studies analyzing purified cell populations from normal and neoplastic human breast tissue at genomic scale and in situ at single cell level and applying mathematical and ecological models for the better understanding of breast tumor evolution. She has also been successful with the clinical translation of her findings including the testing of efficacy of JAK and BET bromodomain inhibitors for the treatment of triple negative breast cancer in clinical trials. Dr. Polyak has received numerous awards including the Paul Marks Prize for Cancer Research in 2011 and the 2012 AACR Outstanding Investigator Award for Breast Cancer Research.