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Silvia Formenti, MD
Professor and Chairman
Department of Radiation Oncology
Weill Cornell Medical College
New York, New York
Goal: To improve response to immune-based therapies so that more patients can benefit from this promising treatment.
Impact: A new class of cancer immunotherapy drugs called check point inhibitors have shown promise in several cancers including some breast cancers. Unfortunately, few breast cancer patients have benefitted thus far. Drs. Formenti and Demaria are investigating ways to improve response to check point inhibitor (CPI) therapy with radiation-induced vaccination. This innovative approach can potentially make immunotherapy a successful and durable treatment approach for breast cancer patients.
What’s next: Having discovered that radiotherapy not only kills tumor cells but also recruits the immune system by triggering signals that mimic an infection, Drs. Formenti and Demaria will determine how to optimize the use of radiotherapy with immunotherapy to improve patient outcome.
Treatments that harness the power of the immune system to fight cancer can be very effective, but most breast cancer patients do not respond to the current check point inhibitors. Drs. Formenti and Demaria are studying the efficacy of combining immunotherapy with radiotherapy, which they have found has the potential to convert a tumor that is not responsive to immunotherapy into a responsive one.
Full Research Summary
Research area: Identifying ways to improve response to immunotherapy in breast cancer patients.
Impact: Immunotherapy—a type of treatment that stimulates a person’s immune system to recognize and destroy cancer cells—is a promising form of treatment. Unfortunately, most breast cancer patients do not benefit from it. Drs. Formenti and Demaria are conducting studies aimed at demystifying the relationship between a patient’s tumor and the immune system. Their findings could pave the way for the development of therapeutic combinations that would more effectively harness the immune system in the fight against breast cancer.
Current investigation: The team has been investigating how radiotherapy could be used in combination with immunotherapy to eliminate breast tumors.
What they’ve learned so far: Drs. Formenti and Demaria have shown that radiotherapy may convert a tumor that isn’t responsive to immunotherapy – sometimes referred to as a “cold” tumor – into a responsive “hot” one. It does this by generating T cells, the cancer-fighting cells of the immune system. Testing in laboratory models has revealed that it is possible to optimize the dose of radiotherapy to achieve this effect.
What’s next: The team will investigate a new platform that will help them optimize the right dose of radiation needed to stimulate the immune response based on the tumor characteristics.
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.