About
Assistant Professor
Department of Radiological Sciences
Cedars-Sinai
Project Title: Targeting Myeloid Inflammation to Reprogram the Immunosuppressive Microenvironment of Breast Cancer
Mentors:
Stephen Shiao, MD, PhD - Cedars-Sinai Medical Center
David Underhill, PhD - Cedars-Sinai Medical Center
Simon Knott, PhD - Cedars-Sinai Medical Center
Jennifer Van Eyk, PhD - Cedars-Sinai Medical Center
Yuan Yuan, MD, PhD - Cedars-Sinai Medical Center
Multidisciplinary Expertise:
Radiation oncology; tumor microenvironment; innate immunity; single-cell and spatial profiling; proteomics; breast oncology
Project description:
Myeloid inflammation is strongly associated with cancer outcomes and therapeutic resistance in patients with breast cancer. Although immunotherapy is an emerging treatment option in triple-negative breast cancer (TNBC), there are no curative treatments after progression on these agents. Using a mouse model of TNBC, we demonstrate that inflammatory myeloid signaling is a novel therapeutic target for overcoming immunotherapy resistance. In this project, we will focus on the role that inflammatory myeloid signaling and neutrophil ferroptosis may play in generating an immunosuppressive tumor microenvironment. We will investigate the role of innate immune sensing of tumors to regulate inflammatory cytokine production. Lastly, we will perform spatial analysis of human TNBC biopsies to validate whether these immunosuppressive mechanisms occur in patients. The ultimate goal of this research is to identify novel therapeutic targets beyond PD-1/PD-L1 in immunotherapy-resistant breast cancers, which is a clinically unmet need in breast oncology.