#targeted-inhibition

#targeted-inhibition

Nicotinamide N-methyltransferase (NNMT) plays a crucial role in high-grade serous ovarian cancer by inducing H3K27me3 hypomethylation, which drives complement secretion from cancer-associated fibroblasts (CAFs). This process attracts immunosuppressive myeloid-derived suppressor cells (MDSCs) to the tumor. The absence of Nnmt in immunocompetent mice hampers tumor growth in various syngeneic models, showcasing an enhancement in CD8+ T cell activation. A high-throughput screening yield led to the development of a potent NNMT inhibitor that effectively reduces tumor burden and metastasis across different mouse cancer models, also improving immune checkpoint blockade efficacy.