Leveraging the metabolic vulnerabilities of macrophages in pancreatic cancer (360G-Wellcome-319019_Z_24_Z)

Pancreatic cancer carries a dismal prognosis, even in the minority of patients who are eligible for surgery. As a result, there is an urgent need to develop novel strategies to improve the quality of life and survival for patients. Immunotherapy has revolutionised the treatment of many cancers, but pancreatic cancer has proven highly resistant; largely due to the tumour microenvironment, which is dominated by immune-suppressive macrophages. The significance of cancer metabolism is now widely recognised but until recently the field has focused on tumour cells. Now, emerging evidence demonstrates the key role that metabolism plays in dictating the functional state of immune cells. This has wide ranging implications and drives the need to deepen our understanding of immunometabolism and how it impacts on treatment resistance. My aim is to deepen our understanding of macrophage biology in pancreatic cancer, use this knowledge to design new therapeutic strategies and to improve the lives of patients with the disease. I will use animal models of immunotherapy resistant and sensitive pancreatic cancer to define the metabolic traits of macrophages during treatment responses. Finally, therapeutics will be administered to exploit metabolic vulnerabilities, targeting macrophage driven immune suppression and promoting their antitumour properties.