Prognostic and Predictive Immune Signatures in Undifferentiated Pleomorphic Sarcomas

Over the past decade, immunotherapy has revolutionized cancer care across many cancer types by harnessing the body’s immune system to fight tumor cells. However, response to current immunotherapies in undifferentiated pleomorphic sarcoma (UPS), one of the most immune-responsive types of sarcoma, remains only of 20 to 40% at best with a significant risk of toxicity from these therapies. Thus, new approaches are needed to improve these responses, through better selection of patients, identification of new immune targets, and combination of treatments. In order to address this critical need, our group has characterized several immune markers and identified prognostic and predictive tumor immune signatures in sarcomas. One is an immune signature based on gene expression of several immune markers and is associated with better survival with immunotherapy in several sarcoma types including UPS. The other is a prognostic immune signature based on characterization of immune cells and immune markers at the protein level which is associated with better survival in localized UPS not treated with immunotherapy. These signatures have been identified using two different methodologies (gene expression versus protein analyses) and in two different settings (treatment with immunotherapy in metastatic sarcomas versus radiation therapy and chemotherapy in localized UPS) and have never been compared and evaluated specifically in UPS samples. This proposal builds upon our expertise of immune signatures in UPS in order to characterize immune markers through these two approaches (gene expression and protein expression signatures) in two cohorts of UPS samples: (1) a cohort of patients treated with immunotherapy and (2) a cohort of patients with localized UPS treated with standard-of-care chemotherapy and/or radiation therapy. Additionally, using these same techniques, we will increase the number of immune markers that we previously studied with both techniques to identify new potential immune targets to improve responses with these treatments. We expect to determine which method of evaluation is more precise for identification of patients that are more likely to have benefit from each treatment modality (immunotherapy, chemotherapy, radiation therapy), from a combination of these treatments, or from new immune therapies that are being developed. This will allow us to understand why some patients benefit from immunotherapy while others do not, as we work toward our goal of identifying potential new targets to improve immunotherapy efficacy.