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iwCLL 2025 | Cholesterol metabolism and immune dysfunction in CLL
Helga Simon-Molas, PhD, Amsterdam University Medical Center, Amsterdam, Netherlands, discusses the role of fatty acids and cholesterol in chronic lymphocytic leukemia (CLL). In healthy cells, fatty acids are crucial for T-cell activation, while cholesterol is essential for T-cell proliferation. In CLL patients, a lack of cholesterol and accumulation of triacylglyceride impede proliferation and immune synapse formation. This interview took place at the biennial International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2025 in Krakow, Poland.
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Transcript
Our recent publication is actually describing the role of, on one side, fatty acids and on the other side, cholesterol, for the function of T-cells. And when we started this project, we actually realized that there was not a lot known in healthy T-cells even. So we applied lipidomics, RNA sequencing, functional studies, to really put together information to describe for what a healthy T-cell is using lipids...
Our recent publication is actually describing the role of, on one side, fatty acids and on the other side, cholesterol, for the function of T-cells. And when we started this project, we actually realized that there was not a lot known in healthy T-cells even. So we applied lipidomics, RNA sequencing, functional studies, to really put together information to describe for what a healthy T-cell is using lipids. And then the conclusion is that fatty acids are mostly used for T-cell activation, while cholesterol is very important for T-cell proliferation. And what’s very clear in the T-cells from CLL patients is that they lack cholesterol, they accumulate a lot of triacylglyceride, so it’s very difficult to burn fat, but they don’t have cholesterol and therefore they cannot proliferate easily, and most importantly they cannot form proper immune synapses, which is something that was described already in 2008 in CLL that we know this is happening. There’s not proper immune synapses in the patients and we think that maybe the lack of cholesterol is behind this observation.
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