Ribosomes are found in every living cell on Earth — but for decades, the conventional wisdom was that these microscopic protein factories were simply unchanging, passive mediators for RNA expression. New research funded by The Mark Foundation upends that assumption and reveals a surprising role for ribosomes: helping cancer cells evade immune detection.
In a new Cell paper, ASPIRE awardees Liam Faller, PhD, and Pia Kvistborg, PhD of the Netherlands Cancer Institute (NKI) show that when cells are exposed to cytokines — a signal of potential danger from the immune system — their ribosomes enter an “alert state.”
“They change the balance towards a type of ribosome that has a flexible arm sticking out, called a P-stalk,” said Faller. “In doing so, they become better at showing themselves to the immune system. Understanding the ribosome’s role in this process could help us improve existing and emerging immunotherapies.”
The Genesis of a Breakthrough
The project was loosely conceived in 2019, when The Mark Foundation’s Head of Preclinical Discovery,
Becky Bish, PhD, visited NKI as part of the foundation’s ongoing outreach to researchers around the globe.
“Cancer research in the Netherlands is especially strong, and NKI is a powerhouse,” she said. “We’re proud to have funded five projects there so far.”
While at NKI, Bish met with Faller, an expert in RNA biology, and Kvistborg, an immunologist specializing in T cell responses in cancer. The two scientists presented an unusual question: what if ribosomes are integral to T cell recognition of tumors?
At the time, Faller and Kvistborg (who has since left NKI to take on a role at Neogene Therapeutics) didn’t have the resources to take the idea further. Securing funding for unconventional research can be challenging, as traditional funding mechanisms often prioritize projects with well-established hypotheses and predictable outcomes.
However, The Mark Foundation recognizes that transformative breakthroughs often arise from exploring uncharted territory. Bish saw the idea’s potential and encouraged Faller and Kvistborg to apply for an ASPIRE Award, which they were granted in 2021. For the investigators, the award was a game-changer.
“It is rare nowadays that researchers are given a bit of freedom in projects,” explained Faller. “The ability to be flexible with your budgets is very under-rated, especially considering how unpredictable fundamental science is.”
The Power of Fundamental Research
Faller and Kvistborg’s work offers both profound insights into ribosomes and new pathways for cancer research. By modulating the process through which different populations of ribosomes may act to “hide” cancer cells, scientists could potentially make cancer cells more visible to the immune system and improve the efficacy of immunotherapies.
The results, explained Bish, show why it’s so important to support scientific projects that span the research lifecycle.
“There’s still so much that we don’t know about how cells and the immune system work,” she said. “It’s important to support fundamental research so that down the road, we can use those insights to develop new therapies.”