Immune cells rely on two distinct pathways to generate acetyl-CoA, a crucial metabolite needed to combat infections and cancer, according to recent research. This study could enhance immunotherapy strategies by demonstrating how dietary choices can enhance immune cell capabilities.
Immune cells rely on two distinct pathways to generate acetyl-CoA, a crucial metabolite needed to combat infections and cancer, according to research conducted by scientists at the Van Andel Institute.
The results, published in the Journal of Experimental Medicine, have the potential to advance immunotherapy by revealing how nutritional intake can strengthen the functionality of immune cells.
“Like any efficient system, immune cells have a primary and a secondary plan,” remarked Russell Jones, Ph.D., the leading author of the study and chair of VAI’s Department of Metabolism and Nutritional Programming. “We’ve discovered how these cells utilize a dual approach to guarantee they generate adequate acetyl-CoA to perform their functions and maintain our health. Notably, our findings provide valuable insights that could inform personalized dietary strategies to enhance current cancer therapies.”
Cells produce acetyl-CoA by utilizing nutrients, such as acetate, obtained from food. When a threat is identified, cells attach acetyl-CoA to specific proteins, which unlocks access to the genetic information necessary to combat diseases and infections. A lack of acetyl-CoA hinders the immune system’s capacity to defend the body.
Until this point, it was unclear how immune cells managed their reserves of acetyl-CoA. In their recent study, Jones and his team discovered two pathways for producing acetyl-CoA: a primary pathway known as ACLY and a secondary pathway called ACSS2. While cells generally favor the ACLY pathway, the ACSS2 pathway activates when needed to ensure a consistent supply of acetyl-CoA.
While this type of “metabolic flexibility” has been observed in cancer cells, this is the first instance of such flexibility being demonstrated in immune cells.
The results also highlight the significant link between metabolism and epigenetics, which are processes that influence how DNA instructions are utilized without altering the DNA sequence itself. Errors in epigenetics are well-recognized factors in cancer and serve as critical targets for potential new therapies.
“We pinpointed specific metabolic centers, including ACLY and ACSS2, that regulate cell function through epigenetic mechanisms,” stated McLane Watson, Ph.D., a co-first author of the study and a postdoctoral fellow in Jones’ lab. “This is exciting because these centers could eventually lead to new methods of enhancing cancer immunotherapies by leveraging metabolism to refine epigenetic processes.”
