Stalking ribosomes: How cancer cells pull poker faces

Our immune system is constantly monitoring our body. In order to survive, cancer cells need to evade this inspection. "Making cells more visible to the immune system has revolutionized treatment," says researcher Liam Faller from the Netherlands Cancer Institute. "However, many patients don't respond to these immunotherapies or become resistant." How cancer cells manage to circumvent elimination by the immune system is still a million dollar question though.

Turns out cancer cells might use our very own protein factories to hide. Each of our cells contain a million of these minuscule factories, called ribosomes. Liam: "They make all the protein we need. This job is so essential: all life depends on it! This is why people have always thought that every ribosome is the same, and that they just passively churn out protein as dictated by the cell's nucleus. We've now shown that this is not necessarily the case."

Cells change their ribosomes when they receive a danger signal from the immune system, the new study showed. Liam: "They change the balance towards a type of ribosome that has a flexible arm sticking out, called a P-stalk. In doing so, they become better at showing themselves to the immune system."

Just like the look on someone's face, the surface of a cell gives away a lot about what is happening on the inside. "Cells coat themselves with little chunks of protein, which is how our immune system can recognize them and tell when there is something wrong," Liam explains. "This is an essential part of our immune response. If a cancer cell can block this, it can become invisible to the immune system."

Liam's group has now uncovered a new way in which cancer cells could pull such a poker face: by affecting their ribosomes. Less flexible-arm-ribosomes, means less 'emotions' on their (sur)face. "We are now trying to figure out exactly how they go about this, so we can maybe block this ability," says Anna Dopler, member of Liam's group and closely involved in the project "This would make cancer cells more visible, enabling the immune system to detect and destroy them."

New angles for future cancer therapies aside, Liam is fascinated by ribosomes: "Every single cell that has ever existed in our family tree relied on ribosomes. There is a hypothesis that all of life developed to allow the ribosome duplicate itself. It's a pretty wild idea, but I love it! I have no idea whether it is true, but just the simple fact that there is something that ancient in every one of our cells fills me with awe."

This research was financially supported by NWO Dutch Research Council, The Mark Foundation and KWF Dutch Cancer Society.