Dana-Farber Cancer Institute
Professor of Medicine, Harvard Medical School
Principal Faculty, Harvard Stem Cell Institute
Associate Member, Broad Institute
Co-Leader, Cancer Cell Biology Program
Dana-Farber/ Harvard Cancer Center
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 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.
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.
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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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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