The protein factories of our cells, ribosomes, are much more diverse than we thought they were. Researchers at the Netherlands Cancer Institute have now shown that cancer cells can use ribosomes to boost their invisibility cloak, helping them hide from the immune system.
The findings are published in Cell.
“Inflammatory cytokines are pivotal to immune responses,” the researchers wrote. “Upon cytokine exposure, cells enter an “alert state” that enhances their visibility to the immune system. Here, we identified an alert-state subpopulation of ribosomes defined by the presence of the P-stalk. We show that P-stalk ribosomes (PSRs) are formed in response to cytokines linked to tumor immunity, and this is at least partially mediated by P-stalk phosphorylation.”
“Making cells more visible to the immune system has revolutionized treatment,” explained 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.
Each of our cells contains a ribosome. “They make all the protein we need,” Faller said. “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. “They change the balance toward 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,” added Faller.
“Cells coat themselves with little chunks of protein, which is how our immune system can recognize them and tell when there is something wrong,” Faller explained. “This is an essential part of our immune response. If a cancer cell can block this, it can become invisible to the immune system.”
“We are now trying to figure out exactly how they go about this, so we can maybe block this ability,” said Anna Dopler, a member of Faller’s group and closely involved in the project. “This would make cancer cells more visible, enabling the immune system to detect and destroy them.”
