Co-Leader, Cancer Immunology Program
Professor of Pathology and Radiation Oncology
NYU School of Medicine
New York, NY
Radiation therapy (RT) directed at a tumor causes a series of specific danger signals that activate the immune system around the tumor. Experiments led by Drs. Demaria and Formenti found that RT enhanced the effect of an antibody blocking the immune suppressor protein CTLA-4 in an experimental model of metastatic breast cancer. Importantly, the resulting immune response was not only effective against the primary irradiated tumor, but also prevented lung metastases. In other words, it vaccinated the host against the irradiated tumor and its metastases. This finding is very relevant clinically, since it could be rapidly adopted to treat metastatic cancer patients. In their BRCF research, the investigators are focused on identifying combinations of therapeutic antibodies to neutralize immune-suppressive molecules in the tumor to allow efficient immune response to subsequent radiotherapy. In the last year the research team reported a significant reduction in tumor growth in a model of metastatic breast cancer when antibody-targeted inhibition of two different immune-suppressive molecules was used in combination with radiotherapy. In the coming year they will compare the results obtained with antibodies and newly developed small molecule inhibitors (SMI) to provide necessary data for moving this strategy forward in patients. Preliminary results suggest that the strategy of blocking multiple selected immune inhibitory targets in combination with radiotherapy has the potential to unleash powerful anti-tumor responses and improve the outcome of metastatic breast cancer in the near future.
Sandra Demaria obtained her MD from the University of Turin, Italy, then moved to New York City for postdoctoral training in immunology followed by training in pathology at New York University (NYU) School of Medicine in the anatomic pathology/research residency track. After completing the residency Dr. Demaria remained on the faculty at NYU where she is currently Professor of Pathology and Radiation Oncology. She serves as co-leader of the Cancer Immunology program of NYU Cancer Institute, and is Scientific Director of the Immune Monitoring Core. She is also a member of the Breast Cancer program and an attending pathologist in the breast cancer service. She heads a laboratory studying innovative treatments for metastatic breast and other cancers. Her work is focused on understanding the mechanisms whereby local radiotherapy generates an in situ tumor vaccine, and exploiting this property of radiation to improve the response to immunotherapy. Studies from her lab have demonstrated that local radiotherapy is synergistic with different immunotherapies in pre-clinical breast cancer models. 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. She holds leadership positions in national professional societies, including the Radiation Research Society, where she served as Council member from 2009-2012, and the Society for Immunotherapy of Cancer (SITC) where she currently serves as chair of the Council for Immunotherapy Education and Outreach and as board member.