By: Krissa Smith, Scientific Grants Manager and Nora Disis, Professor
University of Washington School of Medicine
In the fight against breast cancer, a patient’s immune system plays an important role. The immune system can detect and destroy foreign substances or abnormal cells, such as tumor cells. Unfortunately, tumors have developed a number of tricks designed to fool the immune system, escape detection, and even hijack parts of the immune system to promote tumor growth. Researchers are currently investigating the mechanisms that the immune system utilizes to target and kill tumors in an effort to encourage or focus the immune system to kill more or all of the tumor cells, including those tumor cells that have spread elsewhere in the body. To address this important issue, one of the Komen Investigator Initiated Research Grant focus areas this year was directed towards the “Implications of the Immune System in Breast Cancer Biology”. In March, expert researchers and patient advocates met in Dallas to discuss the most competitive applications that targeted the immune system, resulting in grants being selected for funding that focused on novel ways to use the immune system to target the tumor for destruction.
Our complex immune system includes different types of cells with specific functions. Macrophages are an important type of immune cell that engulfs targeted cells or foreign substances by “eating” and destroying them. Dr. Donald McDonnell from Duke University was awarded a grant to study CaMKK2, a protein that is only seen on macrophages and is responsible for protecting the tumor from the immune system. When this protein is blocked in macrophages, the immune system can attack tumors more efficiently. Dr. McDonnell’s team will study how CaMKK2 impacts the immune system and if targeting this protein in a breast cancer setting will impact tumor progression. Since there are already drugs in clinical practice that specifically target the CaMKK2 protein in other disease settings, Dr. McDonnell will be able to quickly evaluate if there is any benefit for breast cancer patients.
A second grant was awarded to investigate a different function of macrophages in breast cancer. Dr. Pamela Ohashi and Dr. Michael Reedijk from the United Health Network in Toronto have proposed to look at novel ways that macrophages interact with the normal cells surrounding the tumor. Their work will investigate the aspects of the immune response that make it easier for tumors to grow. They also aim to resolve whether Notch signaling pathway activation in breast cancer cells is responsible for this permissive immune environment. Notch signaling is important for cell to cell communication and plays an important role in developing organs such as the heart and bones, as well as the development of vital systems in the body such as the nervous and endocrine systems. Importantly, early data shows Notch signaling has an impact on immune cells that interact with the tumor. Dr. Ohashi’s goal is to inhibit Notch in breast cancer and allow the immune system to attack tumor cells more effectively.
Dr. Joseph Baar and his collaborator, Dr. William Storkus, have taken a different approach to the immune system and cancer. They propose to use the immune system to our advantage and attack the blood vessels that supply the tumor with nutrients and oxygen. Using a vaccine that specifically targets tumor blood vessels, Dr. Baar’s team at Case Western Reserve University hopes to encourage the immune system to destroy the important vessel network feeding the tumor, which will lead to cancer cell death and reduced tumor growth.
Through funding the important work proposed in these grants, Komen hopes this research will lead to advances in long-lasting immunotherapy treatment and a better understanding of the impact of the immune system on breast cancer, metastasis and recurrence.
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