Overview
Sandra Demaria, M.D., a native of Turin, Italy, obtained her M.D. from the University of Turin, and then moved to New York 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 NYU School of Medicine (NYU SoM). She remained on the faculty at NYU SoM until 2015 raising to the rank of Professor. She is currently Professor of Radiation Oncology and Pathology at Weill Cornell Medicine in New York City. 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 tumors unresponsive to immune checkpoint inhibitors into responsive ones, a finding being translated in several clinical trials at multiple institutions. 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. Her current work is funded by the US National Cancer Institute and by several private foundations. She has held leadership positions in national professional societies, including the Society for Immunotherapy of Cancer (SITC) where she served on the Board, the AACR Cancer Immunology Working Group Steering Committee, and the Radiation Research Society. She serves in the editorial board of several journals, including The Journal of Immunology, Cancer Immunology Research, Clinical Cancer Research, and Journal for ImmunoTherapy of Cancer.
The Demaria’s lab has a central interest in addressing the molecular mechanisms whereby ionizing radiation modulates tumor immunogenicity, and exploiting this property of radiation to achieve a therapeutic synergy with immunotherapy in pre-clinical tumor models and in cancer patients. We have recently demonstrated that radiation-induced viral mimicry in cancer cells leads to activation of type I interferon via the cGAS/STING pathway. In vivo, this process contributes to the recruitment and activation of conventional dendritic cells type I (cDC1) to the irradiated tumor and promotes cross-priming and activation of tumor-specific T cells. Ongoing work is addressing other pathways that regulate the ability of radiation to generate an in situ tumor vaccine by modulating innate and adaptive immune cells function. In addition, we found that the transcriptional response elicited by radiation-induced DNA damage enhances the expression of immunogenic mutations, and are investigating the radiation-induced changes in the immunopeptidome presented by MHC class I and MHC class II molecules.
Highlights
- 1The Journal of clinical investigation · 2021
- 2Nature medicine · 2018
- 3Nature communications · 2023
Publications
Funding
Active
10 grants- Co-IBCRF-26-053Optimization of immune checkpoint inhibition during radiation-induced vaccination in breast cancerBreast Cancer Research Foundation · 2026–2028
- PIR01CA201246-08Cancer Cell Intrinsic Interferon-I pathway Activation by Fractionated RadiationNational Cancer Institute · 2016–2027· 2 renewals
- Co-IU54CA274291-01Dynamics of Immune Response in Irradiated Rectal CancerNational Cancer Institute · 2022–2027
- Co-ICRI13928Mechanisms of "fragile" intratumoral regulatory T cells supporting anti-tumor immunityCancer Research Institute, Inc. · 2025–2027
- PIR21CA292282-02Precision use of radiation for in situ cancer immunizationNational Cancer Institute · 2025–2027
- Co-IBCRF-24-053Optimization of immune checkpoint inhibition during radiation-induced vaccination in breast cancerBreast Cancer Research Foundation · 2024–2026
- PIW81XWH-19-1-0142Converting HR+ Breast Cancer Into an Individualized VaccineU.S. Department of Defense · 2019–2026
- Co-IW81XWH-19-1-0141Converting HR+ Breast Cancer Into an Individualized VaccineU.S. Department of Defense · 2019–2026
- Co-IW81XWH-21-2-0034Therapeutic targeting of breast cancer and host immune responses at inflection points in the disease trajectoryU.S. Department of Defense · 2021–2026
- Co-IR01CA249615-02PSMA/MR-guided Stereotactic Body Radiotherapy for High Risk Prostate CancerNational Cancer Institute · 2020–2025
Completed grants (28)
- PISCC I14-0043The effects of radiotherapy on the presentation of phosphorylated antigens by cancer cellsStarr Cancer Consortium · 2021–2024
- Co-IBCRF-23-053Optimization of immune checkpoint inhibition during radiation-induced vaccination in breast cancerBreast Cancer Research Foundation · 2023–2024
- PISRA 225860-01Corroboration the efficacy observed in Project Part 1 and exploration of the mechanisms behind these effectsBoehringer Ingelheim Pharmaceuticals, Inc. (USA) · 2022–2024Contract
- Co-IBCRF-22-053Optimization of immune checkpoint inhibition during radiation-induced vaccination in breast cancerBreast Cancer Research Foundation · 2022–2023
- PIS10OD032317-01Hypoxic incubator for physiological cell culture researchOffice of the Director, NIH · 2022–2023
- KPAACR 21-40-12-VANNThe impact of hypoxia on radiation induced anti-cancer immunityAmerican Association for Cancer Research · 2021–2023
- Co-IW81XWH-19-1-0422Targeting ART1, a novel immune checkpoint, for the treatment of lung cancerU.S. Department of Defense · 2019–2023
- KPW81XWH-21-2-0031Therapeutic targeting of breast cancer and host immune responses at inflection points in the disease trajectoryU.S. Department of Defense · 2022–2023 · via Duke University
- Co-IW81XWH1910101Breaking through immune resistance of HR+ breast cancerU.S. Department of Defense · 2019–2023No publications yet
- PIBIP 578201The role of SIRPα blockade in radiation-induced anti-tumor immunityBoehringer Ingelheim Pharmaceuticals, Inc. (USA) · 2021–2022Contract
- Co-IBCRF-20-053Optimization of immune checkpoint inhibition during radiation-induced vaccination in breast cancerBreast Cancer Research Foundation · 2019–2022
- Co-IUL1TR002384-01Clinical and Translational Science Center - UL1National Center for Advancing Translational Sciences · 2017–2022
- PIR01CA198533-05Individualized in Situ Vaccination by Radiation and ImmunotherapyNational Cancer Institute · 2016–2022
- PICFI 212834-01The Joyce and Irving Goldman Family Foundation Grant Award Matched by Chemotherapy FoundationChemotherapy Foundation, Inc. · 2021–2021
- KP18-40-43-LHUIRole of SIRPa blockade in radiation-induced anti-tumor immunityAmerican Association for Cancer Research · 2018–2021Fellowship
- PICFI 181212-02Modulation of Breast Cancer Immunological Microenvironment by Tumor-Derived ExosomesChemotherapy Foundation, Inc. · 2018–2020
- KPAICF 200926-01Role of Exosomes Derived from Irradiated Cancer Cells in Priming of Anti-Tumor T Cells (2019-2020 Funding)American Italian Cancer Foundation · 2019–2020
- KPS10OD023652-01Instrumentation for Ultra-High Resolution MALDI-FT-ICR Imaging CoreOffice of the Director, NIH · 2017–2020Equipment
- KPW81XWH-17-1-0029Adenosine Blockade With Radiotherapy to Enhance Responses of Breast Cancer to Immune Checkpoint InhibitorsU.S. Department of Defense · 2017–2020
- PISRA 191573-01Amendment 2: In situ vaccination by the combination of radiotherapy and intra tumoral LTX-315 in pre-clinical cancer models.Lytix Biopharma AS · 2018–2019Contract
- Co-IBCRF 17-053Optimization of Immune Checkpoint Inhibition During Radiation-Induced Vaccination in Breast CancerBreast Cancer Research Foundation · 2018–2019
- PICUI 191607Genomic instability and inflammation: fighting cancer with its own weaponsCornell University - Ithaca · 2018–2019
- PIEnhancing Radiotherapy-Induced In situ Vaccination by Intratumoral HfO2-NPNanobiotix · 2018–2019Contract
- Co-IBCRF 17-053Optimization of Immune Checkpoint Inhibition During Radiation-Induced Vaccination in Breast CancerBreast Cancer Research Foundation · 2017–2018
- KPW81XWH-11-1-0530Radiation-Induced Vaccination to Breast CancerU.S. Department of Defense · 2016–2018
- PICFI 16030416-02Modulation of Breast Cancer Immunological Microenvironment by Tumor-Derived ExosomesChemotherapy Foundation, Inc. · 2016–2017
- PIK08CA089336-06TUMOR APOPTOSIS AS MAJOR DETERMINANT OF IMMUNOGENICITYNCI · 2001–2006 · via NIH RePORTER
Honors & distinctions
- Damon Runyon Fellowship / Grant · Damon Runyon Cancer Research Foundation · 1989
News mentions
- Combination Radiation with Immunotherapy Shows Promise Against “Cold” Breast Cancer TumorsSeptember 25, 2023
Researchers at Weill Cornell Medicine have discovered that radiation therapy combined with two types of immunotherapy—one that boosts T cells and another that boosts dendritic cells—can control tumors in preclinical models of triple negative breast cancer, a cancer type that’s typically resistant to immunotherapy alone.
- A Potential New Target for Cancer ImmunotherapiesMarch 16, 2022
Tumors can use an enzyme called ART1 to thwart antitumor immune cells, making the enzyme a promising new target for immunity-boosting cancer treatments, according to a study from researchers at Weill Cornell Medicine and Albert Einstein College of Medicine. In the study, published Mar. 16 in Science Translational Medicine, the researchers found strong evidence that ART1, when expressed on tumor cells, can modify a receptor on tumor-fighting immune cells in a way that triggers the death of these immune cells. In animal models of cancer, blocking ART1 increased the presence of the tumor-fighting immune cells within tumors and slowed or stopped tumor growth. “These findings should allow us to add to our medicinal toolkit for enhancing the antitumor immune response, to benefit cancer patients,” said study co-corresponding author Dr. Timothy McGraw, professor of biochemistry and of biochemistry in cardiothoracic surgery and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. “Our main focus in this study was lung cancer, but there is evidence that this immune-evasion mechanism is at work also in other kinds of cancer,” said co-corresponding author Dr. Sandra Demaria, professor of radiation oncology and of pathology and laboratory medicine and a member of the Meyer Cancer Center at Weill Cornell Medicine. “This is an excellent example of how translational science should work. We first found ART1 expressed in the tumors of patients with lung cancer. In the lab, we discovered that ART1 helps to block the anti-tumor immune response, specifically by inducing death of anti-tumor T cells. We then developed a therapeutic antibody that blocks the function of ART1, allows the immune system to fight the cancer and ultimately prolongs survival in tumor models,” said senior author Dr. Brendon Stiles, formerly of Weill Cornell Medicine and now chief of the Division of Thoracic Surgery and Surgical Oncology and associate director of surgical services at…
- Department of Defense Awards Weill Cornell Medicine New Grant for Breast Cancer ResearchDecember 9, 2021
Weill Cornell Medicine has been awarded a nearly $6.5 million, four-year grant from the Department of Defense as part of a multi-institutional Transformative Breast Cancer Consortium.
- Awards and Honors Across Weill Cornell Medicine - January 23, 2019January 23, 2019
Awards, honors, prizes and achievements for the month of January.
Mentoring
- SVSamantha Van NestPostdoc mentee · 2021–2023
- HSHiro SatoPostdoc mentee · 2023–2024
- DSDavid SprottMD mentee · Class of 2026
- DSDiego SialerMD mentee · Class of 2026
- XDXiaoxue DengPostdoc mentee · 2024–2025