Weill Cornell Medical - New York City
Interests: Anti-Tumor T Cell Repertoire, Cancer Immunotherapy, Combinations Of Radiotherapy & Immune Checkpoint Blockade, Mechanistic Links Between DNA Damage Response & Tumor Immunogencity
Work in my laboratory is currently addressing the molecular mechanisms that are responsible for the increased antigenicity and adjuvanticity of cancer cells in irradiated tumors. We have recently identified mutation-generated CD8 T cell epitopes that are selectively induced in irradiated breast cancer cells and we are currently determining their contribution to immune-mediated rejection of irradiated and abscopal tumors in mice models. My lab is also studying the immunological changes in cancer patients treated with radiotherapy and immune checkpoint blockade to identify determinants of response. We have recently identified an immunogenic mutation that is exposed by radiation in a patient with lung cancer who had a complete response to RT and anti-CTLA-4. My lab has recently demonstrated that radiation-induced synergy with immune checkpoint blockade is critically dependent on interferon type I responses induced by cytosolic DNA via the cGAS/STING pathway. Moreover, we have shown that accumulation of cytosolic DNA is regulated by the exonuclease TREX1 and dependent on the radiation dose. Our recent studies in patients support a critical role of interferon type I in radiation-induced in situ vaccination.