Where lipoproteins meet T cells

Summary

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T cells are highly adaptable white blood cells that protect us from infections, cancer, and other threats. To do their job, T cells must rapidly switch from a quiet resting state to an active, energy demanding mode, then shut down once the danger has passed. This delicate balance is essential for health, as uncontrolled T cell activity can lead to chronic inflammation or autoimmune disease.

This thesis explores an underappreciated aspect of T cell biology: how these immune cells use fats and cholesterol carried through the body by lipoproteins such as LDL. While LDL is often labeled “bad cholesterol,” it plays an essential role by delivering cholesterol that cells need to grow, divide, and function. T cells take up LDL using a surface protein called the LDL receptor (LDLR), yet until now, little was known about how this process influences T cell responses.

Using a combination of experimental models and patient samples, including individuals who lack functional LDLR, this work shows that lipoprotein uptake strongly shapes how T cells activate, multiply, and specialize. LDL supports both inflammatory and inflammation-limiting T cell responses and affects the killing ability of cancer-fighting T cells. The research also reveals that drugs developed to lower cholesterol, such as PCSK9 inhibitors, can unexpectedly boost immune function, suggesting new opportunities for cancer immunotherapy.

This work highlights the metabolic flexibility of T cells and shows how their immune behavior is closely tied to lipid uptake and use, opening new therapeutic avenues for cancer, autoimmune, and metabolic diseases.

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