Growth and differentiation factor 15 (GDF15) is a cytokine that is secreted at elevated levels from a variety of cell types including tumor and inflammatory cells. It is secreted at elevated levels in response to various stresses including chronic inflammation, obesity, cardiovascular diseases, cancers, and chemotherapy treatment.
High GDF15 expression is associated with cachexia including loss of appetite, nausea, and weight loss. Blockade of GDF15 has been shown clinically to increase body weight in cancer cachexia patients.
GDF15 expressed by tumors is also able to drive cancer progression by promoting an immunosuppressive tumor microenvironment. This includes a reduction in T cell infiltration and increase in Treg function. High GDF15 expression is seen across a broad range of cancers including gastric, colorectal, pancreatic and prostate, and typically correlates with poor prognosis.