The Role of TGFβ2 and Macrophages in Cancer Cachexia

SUMMARY Cachexia is a significant contributor to increased mortality in various chronic diseases, including cancer. Patients with cancer cachexia experience unintentional body weight loss, which can involve muscle loss, with or without fat mass. The decline in muscle mass not only impairs muscle function, but also diminishes quality of life and raises mortality risk. Our preliminary research has revealed an upregulation of transforming growth factor 2 (TGFβ2) preceding the recruitment of M2 macrophages to the skeletal muscle in cachectic mice. Additionally, we observed that depleting M2 macrophages inhibited the transition from cachexia to severe cachexia by preserving muscle mass and reducing fibrosis. These data highlight the involvement of M2 macrophage activation in cachexia progression with the assistance of TGFβ2. In this proposal, we will investigate the role of TGFβ2 in initiating fibrosis and activating M2 macrophages in the skeletal muscle of cancer cachectic mice. Furthermore, we hypothesize that M2 macrophages act as a pivotal transition point driving the advancement of severe cancer cachexia. The outcomes of this study may uncover a novel mechanism and innovative strategies for the treatment of cancer cachexia.