Grant: Project Grant

Muscle wasting that occurs with cancer is known as cachexia. Cachexia affects the majority of patients with late-stage cancer, and is thought to directly contribute to one-third of cancer deaths. Despite these significant features, cachexia is an understudied entity. Our research focuses on the idea that both tumors release factors that activate some cells of the immune system which, in turn, release other signals that cause the muscles to shrink. Our preliminary data suggest that the immune cell at the "heart" of this process is the myeloid-derived suppressor cell (MDSC). These cells rapidly rise during cancer. On depletion of these cells during our mouse models of cancer, we can eliminate muscle wasting, even though cancer remains. However, some tumors cause cachexia and others do not. we have compared the signals released by each of these tumors and identified a family of messengers that seem to play an important role in activating these cells. These messengers use the same signaling system called CSF2RB1. In this grant, we will characterize the role of these CSF2RB1 messengers during cachexia using functional assays and state-of-the-art technologies, including single cell sequencing. Finally, we determine the mechanisms by which these signals cause muscles to shrink in cachexia. Understanding how these immune cells tell the heart and muscles to shrink can help us to prevent or revert these processes and improve the lives of people with muscle-wasting cancer.