| Description |
The tumor microenvironment (TME) is very complex and important due to its ability to influence the response of therapies on tumors. Immune cells infiltrate the TME and secrete inflammatory cytokines, such as interferon-gamma (IFNg), which help activate the immune system. This activation leads to an anti-tumor response within the tumor. Recent evidence, however, suggests that tumor cells can harness IFNg to enhance growth and tumor burden. Novel data from our lab indicates that IFNg, mediates the metabolic reprogramming of melanoma cells by inducing the essential NAD salvage pathway enzyme Nicotinamide phosphoribosyltransferase (NAMPT) (7). NAMPT is found in all cells during normal cell homeostasis making it difficult to target in cancer cells only. Our lab discovered that IFNg signaling upregulates NAMPT in mouse melanoma cells, which plays important roles in cell proliferation and cell survival. Further, our data show that IFNg also upregulates NAMPT in a leukemia cell line: C1498. This provides evidence that other cancer cell types respond to IFNg by increasing NAMPT to improve their fitness as a potential mechanism of resistance against immune signaling. A better understanding of the mechanisms regulating NAMPT for different types of cancer can potentially lead to improved therapeutic targets. Collectively, this work gives insight into the pro-tumorigenic role of IFNg-induced NAMPT in various cancer cells which can be used to improve immune-therapies, such as the combination of compounds such as NAMPT inhibitors, stimulators of interferon genes protein (STING) agonists, and other pathway inhibitors. |
