Kornelia Polyak, MD, PhD
Professor of Medicine, Harvard Medical School
Principal Faculty, Harvard Stem Cell Institute
Associate Member, Broad Institute
Co-Leader, Dana-Farber Harvard Cancer Center, Cancer Cell Biology Program
Understanding the timing and underlying mechanism by which cancer cells escape the immune system to become invasive and metastatic.
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.
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.
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.
We could not do innovative pioneering work without organizations like BCRF. – Dr. Polyak
Kornelia Polyak, MD, PhD, is a Professor of Medicine at Dana-Farber Cancer Institute, Harvard Medical School and is an internationally recognized leader of the breast cancer research field. Dr. Polyak’s laboratory is dedicated to the molecular analysis of human breast cancer with the goal improving 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 has 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 to apply 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 JAK2 and BET bromodomain inhibitors for the treatment of triple-negative breast cancer in clinical trials. Dr. Polyak have received numerous awards including the Paul Marks Prize for Cancer Research in 2011, the 2012 AACR Outstanding Investigator Award for Breast Cancer Research, and the Rosalind Franklin Award in 2016. She is also a 2015 recipient of the NCI Outstanding Investigator award.
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