Defining immune landscapes and IL-1RAP driven myeloid immunosuppression in Ewing sarcoma
Ewing Sarcoma (EWS) is a rare and aggressive cancer that primarily affects children and young adults. This tumor can arise in bones or soft tissues and is particularly dangerous when it spreads to other parts of the body (metastasis) or returns after treatment (relapse), with survival rates dropping below 30%. No progress has been made for these patients in decades, despite ongoing clinical trials, and these patients are required to endure intense chemotherapy every other week with significant short- and long-term side effects. While immunotherapy has revolutionized treatment options for many adult cancers, its effectiveness has been disappointingly limited in pediatric tumors such as EWS. Researchers believe this lack of response may be linked to the unique biology of pediatric cancers, including a lower number of mutations that could generate effective targets for immune attack. Though EWS has been thought to have minimal immune cell infiltration, new studies suggest that the immune environment may be more complex, potentially hiding opportunities for new treatments. Understanding this intricate immune landscape is crucial for uncovering barriers to effective immunotherapy and identifying new avenues for innovative therapies that will give these patients a better chance of long-term survival.
Project Goals
The aim of this project is to comprehensively examine the immune microenvironment of Ewing Sarcoma (EWS) using advanced techniques and a valuable biorepository of human tumor samples, generously gifted by our patients and their families. By employing a multimodal approach, we will characterize the diverse immune cell populations present in EWS tissues and explore their functional roles and interactions within the tumor environment. Specifically, we will investigate how different immune cell types interact with each other and will correlate these findings with patient outcomes. Understanding these immune dynamics is crucial, as different immune cell types can either support or hinder effective tumor responses. One key focus will be on the role of a protein called IL1RAP, which may influence immune system suppression in the tumor microenvironment, and may be targeted by therapies in the future. Ultimately, this research seeks to reveal the immune signatures associated with better prognoses and identify potential therapeutic targets for improving treatment outcomes. By deepening our understanding of the immune landscape in EWS, we hope to pave the way for more effective immunotherapy strategies that could benefit young patients fighting this challenging disease.
