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Sandra Demaria, MD
Professor and Chairman
Professor of Pathology and 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 checkpoint inhibitors have shown promise in several cancers including some breast cancers. Unfortunately, few breast cancer patients have benefitted thus far. Drs. Demaria and Formenti are investigating ways to improve response to immunotherapies such as checkpoint inhibitor (CPI) therapy with radiation treatment. 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. Demaria and Formenti 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 immunotherapy with checkpoint inhibitors. Drs. Demaria and Formenti 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. Checkpoint inhibitors (CPI) are a new calls of immunotherapy agents that work by preventing tumor cells from shutting down tumor immune response. Several CPI drugs are approved for treatment of various types of cancers, including some breast cancers, however, their effectiveness in breast cancer has been disappointing overall. Research by Drs. Demaria and Formenti has shown that radiation therapy has the potential to convert a nonresponsive (immunogenically cold) tumor into responsive (immunogenically hot) one.
Current investigation: The team has developed a platform to study the immunogenic effects of radiotherapy. They will use this platform to examine individual patients’ tumors to determine the tumor factors that mediate an optimal response to radiotherapy.
What they’ve learned so far: Drs. Demaria and Formenti have shown that radiotherapy may convert a tumor that is unresponsive 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. In the last year, Drs. Demaria and Formenti have developed patient-derived tumor organoids from different types of breast cancers. This approach allows them to study the response of breast tumors to different doses of radiotherapy in the laboratory.
What’s next: The team will utilize patient-derived tumor organoids to optimize radiotherapy doses and to study radiation induced pro-immunogenic responses that occur in irradiated tumors. They will also study how circulating exosomes can be used as biomarkers of radiotherapy-induced pro-immunogenic responses. These studies provide a critical step towards developing precision radiotherapy and determining how it can be used to enhance response to immunotherapy.
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.