Institution: VIB (Center for Cancer Biology). Leuven, Belgium
Team: Laboratory of Tumor Inflammation and Angiogenesis.
PI: Massimiliano Mazzone
Objectives: Metabolic competition within the tumor microenvironment is a key hallmark of cancer progression and it can influence the growth and the survival of both cancer cells and tumor stromal cells. We studied Glutamate dehydrogenase 1 (GLUD1), an enzyme that catalyzes the oxidative deamination of glutamate to α-ketoglutarate, and we demonstrated that upon the inhibition of GLUD1 in macrophages we could observe an increase in glutamine level. In a context of immune checkpoint treatments, the increase in glutamine availability can lead to T cell activation and, thus, boost the immune response. Expected Results: the goal of the project is to reprogram the tumor microenvironment via metabolic editing of cancer cells and/or TAMS in order to improve the efficacy of cancer immunotherapies, both adoptive cell transfer and immune checkpoint inhibition.