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With a little help from our cholesterol

Professor Michael Dustin of the Kennedy Institute of Rheumatology comments on new research into boosting the immune system's response to cancer with cholesterol, in Nature

The ability to stimulate our immune system in the fight against cancer or autoimmune diseases is now a reality, but there are still challenges to overcome and further medical advances to pursue.

With 50% of people born after 1960 set to be diagnosed with some form of cancer during their lifetime, developing successful treatments is a key focus of biomedical research.

 

This work may give a new meaning to "good" cholesterol.
- Professor Michael Dustin

New research also published in Nature proposes a way to boost the function of anti-tumour T cells, using a metabolic trick to increase the level of cholesterol in the cells' membranes, bringing new hope to patients worldwide.

T cells determine the specificity of our immune response to foreign substances in the body, like tumour cells. They sense these substances through clusters of T-cell receptor proteins on a cell's surface, which then initiate T cell activation. This activation can be enhanced by a number of factors or substances, namely cholesterol on the cell membrane.

The research team has used a drug to stop cholesterol being converted into cholesterol ester, which led to higher cholesterol levels in the cell membrane of killer T cells, promoting clustering of T-cell receptors that bind to the surface of tumour cells. Higher-membrane cholesterol also led to an increase in the speed at which the T cell and tumour cell form a point of embrace called the immunological synapse, a crucial step in our immune response. Together, these factors promoted the release of molecules that trigger tumour-cell death.

"This work may give a new meaning to "good" cholesterol. The potential to combine this approach with an established immunotherapy like anti-PD-1 is exciting as drug combinations offer advantages for targeting heterogeneous or rapidly mutating disease agents- like cancer and viruses", 

Professor Dustin 's research at the Kennedy focuses on immunological synapse (IS), a term he first coined to describe the embrace between T cells and B cells that is necessary to mount an immune response. His current work aims to improve vaccines and immunotherapy by revealing the composition of particular structures related to immunological synapses, defined as synaptic ectosomes, as well as identify ways to manipulate their formation.

 

Image copyright: Nature.