Grant: Doctoral Research Award: Canada Graduate Scholarships

Cancer-associated cachexia is a disorder characterized by the progressive loss of skeletal muscle mass and adipose tissue in response to malignant growth. Despite one-third of cancer patients being affected by the syndrome, there are no effective treatment options. This is largely because of our lack of knowledge regarding the mechanism behind cancer cachexia. Recently, Granulocytic myeloid-derived suppressor cells (gMDSCs) have been proposed as a candidate responsible for signaling metabolic changes leading to cachexia. gMDSCs are immunosuppressive cells and are known to expand under inflammatory conditions, such as tumor growth. In order to improve our understanding, we characterized the role of gMDSCs under cachectic conditions. We have shown significant expansion of gMDSCs in our cachectic mouse model. Importantly, depletion of this immune population completely protected against heart and skeletal muscle loss. Comparing cachectic conditions with non-cachectic conditions, we saw increased levels of IL-5, a CSF2RB ligand. CSF2RB-deficiency prevented the development of LLC-induced cachexia, but without affecting gMDSC expansion. Whether CSF2RB-deficiency affects gMDSC function is unknown. Based on these results, our goal here is to understand how CSF2RB-ligands influence gMDSC function in cancer-associated cachexia. By doing so, we hope to provide insights into the cachectic mechanism of gMDSCs, which can lead to the development of new therapies for this devastating disorder.