A new perspective on the role of the signal molecule adenosine

Imagine you are an immune cell that has just received instructions to fight and needs to become activated. For that, you need energy and nutrients. But how much should you ask for? How does a cell measure its own activity? And how does it also determine whether it has enough energy to sustain that activity? The authors found that adenosine can do exactly this. Adenosine is produced during so-called methylation processes in the cell, which are essential for almost everything the cell does. The more active a cell is, the more methylation occurs and the more adenosine is produced.

To keep this activity going, adenosine must be recycled for another round of methylation, but this requires energy. If there is not enough energy available, adenosine becomes a kind of indicator of the balance between activity and nutrient supply. And this is where it gets particularly interesting—if you are a truly important cell within the organism, such as an immune cell on which survival depends, you have the privilege of demanding more nutrients when your activity increases. You do this by sending out a signal—adenosine. This signal suppresses the activity of surrounding, less privileged cells, causing them to yield their nutrients to you. Simply put, you are more important.

In this article, the authors propose a new view of how privileged and non-privileged cells handle adenosine. Non-privileged cells are set up so that they do not release adenosine when they lack sufficient energy; instead, they reduce their activity to conserve it. This is very important during an immune response, when energy should be directed toward the immune system. However, this mechanism is also used by the brain, which is another privileged organ.

Unfortunately, it appears that cancer cells can also exploit this mechanism—not only to steal nutrients from their surroundings but also to suppress the immune response against them. It is known that adenosine levels are higher in tumors and that it likely dampens immune responses (thus often complicating new immunotherapies being introduced). However, until now, the mechanism of adenosine production proposed by the authors had not been considered.