Cancer cells may use our very own protein factories to hide from the immune system.
Researchers at the Netherlands Cancer Institute, led by Liam Faller, have discovered that cancer cells can manipulate their ribosomes to evade the immune system. By altering the ribosomes’ structure, cancer cells become less detectable, hindering the immune response. “These findings make us change how we think about ribosomes.”
Immune Evasion in Cancer
Our immune system is constantly on the lookout for threats in our body. For cancer cells to survive, they need to avoid being detected. “Making cells more visible to the immune system has revolutionized treatment,” says Liam Faller, a researcher at the Netherlands Cancer Institute. “However, many patients don’t respond to these immunotherapies or become resistant.” The question of how cancer cells evade the immune system remains a significant challenge.
Ribosome Diversity and Cancer Cell Adaptation
It turns out that cancer cells may be using our own protein factories to hide. Each of our cells contains millions of tiny factories called ribosomes. “They make all the protein we need. This job is so essential: all life depends on it!” Liam explains. “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. According to 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.”
Cancer Cells’ Camouflage Tactics
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.”
“These findings make us change how we think about ribosomes.”
Innovations in Cancer Therapy and Ribosome Research
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.”
Reference: “P-stalk ribosomes act as master regulators of cytokine-mediated processes” by Anna Dopler, Ferhat Alkan, Yuval Malka, Rob van der Kammen, Kelly Hoefakker, Daniel Taranto, Naz Kocabay, Iris Mimpen, Christel Ramirez, Elke Malzer, Olga I. Isaeva, Mandy Kerkhoff, Anastasia Gangaev, Joana Silva, Sofia Ramalho, Liesbeth Hoekman, Maarten Altelaar, Roderick Beijersbergen, Leila Akkari, Jonathan Wilson Yewdell, Pia Kvistborg and William James Faller, 21 October 2024, Cell.
DOI: 10.1016/j.cell.2024.09.039
This research was financially supported by NWO Dutch Research Council, The Mark Foundation and KWF Dutch Cancer Society.
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