The variety of protein-producing structures in our cells is much broader than previously understood. Researchers have discovered that cancer cells can utilize these structures, known as ribosomes, to enhance their ability to avoid detection by the immune system.
The variety of protein-producing structures in our cells is much broader than previously understood. Researchers from the Netherlands Cancer Institute have discovered that cancer cells can utilize these structures, known as ribosomes, to enhance their ability to avoid detection by the immune system. The team shares their discoveries today in Cell. “These findings challenge our previous perceptions of ribosomes,” they state.
Our immune system is constantly vigilant, keeping tabs on our bodies. To thrive, cancer cells must find ways to elude this scrutiny. “Enhancing the visibility of cells to the immune system has dramatically changed treatment protocols,” explains researcher Liam Faller from the Netherlands Cancer Institute. “Nevertheless, many patients either do not benefit from these immunotherapies or develop resistance to them.” The strategy cancer cells use to escape destruction by the immune system remains a significant mystery.
Interestingly, cancer cells may exploit our own protein-producing structures to conceal themselves. Each cell contains about one million of these tiny factories, called ribosomes. Liam notes, “They produce all the proteins necessary for life. This function is critical: life depends on it! This is why it was generally assumed that all ribosomes are identical, passively producing proteins as directed by the cell’s nucleus. We’ve now demonstrated that this is not always the case.”
The recent study revealed that cells alter their ribosomes in reaction to signals of danger from the immune system. Liam explains, “They adjust the proportion of a specific type of ribosome that has a flexible extension known as a P-stalk. By doing this, they improve their visibility to the immune system.”
The exterior of a cell can reveal much about its internal state, much like a person’s facial expression. “Cells cover themselves with small protein fragments, allowing the immune system to identify and react when something is amiss,” Liam clarifies. “This is crucial for our immune response. If a cancer cell can inhibit this process, it becomes invisible to the immune system.”
Liam’s team has identified a novel mechanism that cancer cells could employ to maintain this veil: by manipulating their ribosomes. Fewer flexible-arm ribosomes correspond to fewer ‘signals’ on their exterior. “We are currently investigating how this manipulation occurs, with the aim of potentially inhibiting this capacity,” says Anna Dopler, a member of Liam’s team who is deeply involved in the project. “This would increase the visibility of cancer cells, allowing the immune system to recognize and destroy them.”
Beyond opening new pathways for future cancer treatments, Liam finds ribosomes utterly fascinating: “Every cell in our ancestral lineage has depended on ribosomes for survival. There is a hypothesis suggesting that all life evolved to facilitate the replication of ribosomes. It’s a rather bold idea, but I find it captivating! While I can’t confirm its validity, the presence of something so ancient in all our cells is awe-inspiring.”
This research received financial support from the NWO Dutch Research Council, The Mark Foundation, and the KWF Dutch Cancer Society.
