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Sandra Demaria, MD
Professor and Chairman
Professor of Pathology and Radiation Oncology
Weill Cornell Medical College
New York, New York
- Seeking to understand the interactions between breast cancer and the patient's immune system.
- Studies are ongoing to test the combination of radiation therapy with immunotherapy.
- These studies will help to identify strategies that can improve response to immunotherapy and extend lives of patients with metastatic breast cancer.
Treatments that enlist the help of the immune system to fight cancer are very effective, but few breast cancer patients respond. Drs. Demaria and Formenti have shown that radiotherapy not only kills tumor cells but also recruits the immune system by triggering signals that mimic an infection. They are conducting studies to turn this radiation-induced inflammatory response into a powerful response that eliminates the tumor.
Full Research Summary
Harnessing the patient's own immune system against an established cancer has proven to be a successful strategy for some patients. Within the last five years, several immunotherapy drugs have been approved for use in patients with melanoma, lung cancer, and a few other malignancies. These drugs, called checkpoint inhibitors, work by preventing tumor cells from shutting down the immune response.
Recent trials have shown that some patients with metastatic or triple negative breast cancers also respond to these therapies. Unfortunately, most breast cancer patients will not benefit from current immunotherapies. Improving our understanding of the relationship between an individual patient’s tumor and the immune system is urgently needed to develop therapeutic combinations to treat breast cancer.
Drs. Demaria and Formenti have shown that radiotherapy elicits signals that mimic a viral infection and activates anti-tumor immunity. The team has shown that blocking multiple immune inhibitory targets in combination with radiotherapy has the potential to unleash powerful anti-tumor responses. The radiotherapy dose can be optimized to achieve this effect, and the team has identified specific characteristics of the cancer cells that are important for the success of this response.
In the coming year, the team will investigate a new platform for the ability to predict the best treatment for a given patient’s tumor with the goal of developing a personalized treatment strategy.
Collectively, Drs. Demaria and Formenti are working to find new ways to break the immunosuppressive actions of tumor cells and advance our understanding of the interaction between breast cancer and the patient's immune system to improve patient outcomes.
Sandra Demaria, MD, a native of Turin, Italy, obtained her MD from the University of Turin. She then moved to New York City for her post-doctoral training in immunology as a Damon Runyon-Walter Winchell Cancer Research Fund awardee, followed by a residency in anatomic pathology at New York University School of Medicine. She remained on the faculty at NYU School of Medicine, where she was an attending pathologist in the breast cancer service, an independent investigator and co-leader of the Cancer Immunology program of NYU Cancer Institute until 2015, raising to the rank of Professor. She is currently Professor of Radiation Oncology and Pathology at Weill Cornell Medicine Medical College where she leads a NIH-funded laboratory.
Dr. Demaria is internationally known for her studies demonstrating the synergy of local radiation therapy with different immunotherapeutic agents in pre-clinical models of cancer. She was the first to show that radiotherapy can convert breast tumors unresponsive to immune checkpoint inhibitors into responsive ones. She has been working in partnership with Dr. Silvia Formenti for the past decade to develop a novel treatment paradigm exploiting the immune adjuvant effects of radiotherapy and translate the pre-clinical findings to the clinic.
Dr. Demaria's current work is aimed at identifying the molecular mechanisms that regulate ionizing radiation’s ability to generate an in situ tumor vaccine in preclinical tumor models as well as cancer patients treated in clinical trials testing various combinations of radiation and immunotherapy. As a breast cancer pathologist Dr. Demaria has also studied the immunological microenvironment of breast cancer in patients, and therapeutic strategies to modulate the immune infiltrate in preclinical breast cancer models.
She holds leadership positions in national professional societies, including the Society for Immunotherapy of Cancer (SITC) where she currently serves on the Board, and is a member of the Steering Committee of AACR Cancer Immunology Working Group. She is also an elected member of the European Academy for Tumor Immunology (EATI), and serves in the editorial board of several journals, including Radiation Research, The Journal of Immunology, Clinical Cancer Research, and Journal for ImmunoTherapy of Cancer.