Clinical Instructor
Department of Radiation Oncology

Project title: Targeting radiation-induced myeloid cells in undifferentiated pleomorphic sarcoma

Antoni Ribas, MD, PhD – UCLA
William McBride, PhD – UCLA
Fritz C. Eilber, MD - UCLA

Multidisciplinary Expertise:
Sarcoma, Radiation Oncology, Tumor Immunology & Immunotherapy, Macrophage and T cell Biology, Translational Clinical Trials, Murine Tumor Models

Project Description:
Up to 50% of patients with soft tissue sarcoma ultimately develop local disease failures or incurable distant metastases despite radiotherapy (RT) and surgery. The central premise of this proposal is that myeloid cells regulate the local and systemic anti-tumor effects of radiotherapy in undifferentiated pleomorphic sarcoma (UPS), a common soft tissue sarcoma. We will utilize both syngeneic murine models of UPS and patient specimens from an ongoing clinical trial to study these phenomena. We propose to characterize RT-induced myeloid cells in UPS and their impact on (1) local tumor control and (2) systemic anti-tumor T cell responses. Our approach will include high-dimensional cytometry, single cell proteomics, and multiple strategies to target myeloid subsets in combination with focal RT in murine models. We envision these studies will inform design of a clinical strategy to target myeloid subsets in combination with RT to improve local control, reduce metastases, and prolong survival.