Johns Hopkins University Baltimore, Maryland
Dana and Albert “Cubby” Broccoli Professor of Oncology Deputy Director, The Sidney Kimmel Comprehensive Cancer Center Co-Director of the Gastrointestinal Cancers Program
Developing methods to optimize the use of immunotherapy for the treatment of metastatic breast cancer.
Immunotherapy utilizes the power of a patient’s immune system and offers new promise for some breast cancers. Although newer immune therapies that target the PD-1/PD-L1 pathway have improved breast cancer outcomes for some patients with advanced breast cancer, most do not benefit from these agents. Understanding which patients benefit—why some do, and others do not—is key to their broader clinical benefit. While PD-L1 is a clinically relevant biomarker of immune activation across at least two subtypes of advanced breast cancer, studies showed that the tumors lose their immune reactivity as breast cancer progresses. Dr. Jaffee and her team are examining the expression of PD-L1 and other immune markers in breast cancers that have metastasized to determine whether the profile of immune markers is different at different sites of metastasis. The results of their studies will provide valuable insights to inform treatment decisions and optimize the use of immunotherapy for treating metastatic breast cancer patients.
Previous clinical trial results showed that targeting PD-1/PD-L1 could provide durable clinical responses in small numbers of advanced breast cancer patients. However, it remains unclear how immune biomarkers change as the disease progresses, what role they may play in the process, and their association with different sites of metastases. To investigate these questions, Dr. Jaffee’s team has collected a series of matched primary and metastatic breast cancer samples from different metastatic sites i.e., liver, brain, etc. To date, they have observed distinct changes in immune cells—there is a paucity of lymphocytes but an increase in CD63+ and CD163+ macrophages—and the distribution of macrophages is different in brain compared to liver metastases.
Dr. Jaffee will validate the recent findings and continue to analyze immune biomarkers (including PD-1/PDL-1) in this set of matched primary and metastatic breast tumors. By several techniques including digital scanning and image analyses, the team will conduct a robust examination of the spatial distribution of immune cells by metastatic site and determine the relationship between these cells and the expression of PD-L1 or other immune checkpoint molecules in TNBC. They hope to gain a deeper understanding of how the tumor immune microenvironment evolves with disease progression and how they are associated with breast cancer metastases at different sites.
Elizabeth M. Jaffee, MD, FAACR, FACP is an internationally recognized expert in cancer immunology and pancreatic cancer. She is Deputy Director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Co-Director of the Skip Viragh Pancreatic Cancer Center, and Associate Director of the Bloomberg Kimmel Institute for Cancer Immunotherapy. Her research focus is on developing novel immunotherapies for the treatment and prevention of pancreatic cancer.
Dr. Jaffee is a Past President of American Association of Cancer Research and has served on a number of committees at the National Cancer Institute including co-chair of the Blue-Ribbon Panel that provided scientific advice to Vice President Biden’s Moonshot Initiative. She currently serves as chair of the National Cancer Advisory Board and Chief Medical Advisor to the Lustgarten Foundation for Pancreatic Cancer Research. She is the inaugural Director of the new Convergence Institute at Johns Hopkins and was recently elected to the National Academy of Medicine and is a Fellow of the American College of Physicians.
2014
The Clinique Award
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