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Silvia Formenti, MD
Professor and Chairman
Department of 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. Formenti and Demaria 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. Formenti and Demaria 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. Formenti and Demaria 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.
Dr. Silvia C. Formenti, an international expert in the use of radiation therapy for the treatment of cancer, is Chair of the newly established Department of Radiation Oncology at Weill Cornell Medical College and Radiation Oncologist-in-Chief at New York-Presbyterian/Weill Cornell Medical Center. A prolific researcher, she has published over 180 papers recognized by high impact journals like JAMA, Journal of Clinical Oncology, Lancet Oncology, Science etc.
During the past twelve years, Dr. Formenti has introduced a paradigm shift in radiation biology, by elucidating the role of ionizing radiation on the immune system, and demonstrating efficacy of combining radiotherapy with immunotherapy in solid tumors. She has translated her preclinical work to clinical trials in metastatic breast cancer, lung cancer and melanoma. She has introduced the concept of recovering an immunological equilibrium in metastatic disease, by converting a metastasis into an in situ, individualized vaccine. In the presence of immune checkpoint blockade (anti-CTLA-4 , anti-PDL-1) the irradiated tumor becomes an immunogenic hub, similar to a vaccine. Once immunized against one site, the host develops an anti-tumor immune response capable to reject the other metastases. In some patients with metastatic disease refractory to standard treatment the combination of local radiation and immune checkpoint blockade has resulted in durable complete remissions, sustained for years after treatment. Her work has opened a new field of application for radiotherapy, whereby localized radiation can be used as an adjuvant to immunotherapy of solid tumors and lymphomas.