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By: Cara Michelle Miller
Cholesterol may boost the immune system’s ability to fight and target tumors.
A recent study from the Icahn School of Medicine at Mount Sinai in New York reveals that cholesterol plays a crucial role in the function of dendritic cells, the immune cells that help the body recognize and fight cancer.
Dendritic cells act as the body’s scouts, patrolling for threats like cancer cells and alerting the immune system to take action. To do this effectively, dendritic cells must mature and communicate with other immune cells—a process fueled by cholesterol.
“We identified the metabolism of cholesterol as an essential pathway in mature dendritic cells,” the study authors wrote. This discovery highlights cholesterol’s important role in dendritic cell growth, a key process in launching an immune attack on tumors.
How Cholesterol Fuels Immune Cells
The study, published in Nature Immunology, shows that cholesterol helps form small, cholesterol-rich structures on the surface of dendritic cells called lipid nanodomains. These hubs are vital for signaling the immune system to recognize and fight cancer.
All cells in the body contain cholesterol for proper function. This cholesterol can be obtained through the diet, or the body may make its own cholesterol.
Without enough cholesterol, the researchers observed that these hubs could not form properly, preventing dendritic cells from growing and limiting their ability to alert the immune system, ultimately impairing the body’s ability to detect and fight cancer.
Dendritic cells use cholesterol from both neighboring (often dead or dying) cells and their own production to build structures that strengthen immune responses.
“We show that mobilization of newly acquired and synthesized cholesterol that is then trafficked and organized into lipid nanodomains on the plasma membrane is essential for cDC [dendritic cell] maturation,” the authors wrote.
Simply put, cholesterol creates these communication hubs and ensures dendritic cells grow properly and can support a stronger immune response to cancer, particularly lung cancer, the authors noted.
A Key Regulator of Cholesterol
The researchers also discovered that manipulating the cholesterol metabolism within dendritic cells could strengthen the body’s natural immune defenses against cancer.
They identified a protein called AXL, known for its role in immune regulation, as a key regulator of cholesterol metabolism in these cells. The Mount Sinai team uncovered how AXL acts like a brake on the cholesterol system, slowing down the movement of cholesterol and hindering dendritic cells from growing properly.
AXL suppresses the movement of cholesterol and inhibits the assembly of lipid nanodomains, the study authors noted. This means that AXL slows down the process that helps dendritic cells grow and communicate effectively with the immune system.
Blocking AXL made dendritic cells mature faster and trigger stronger immune responses, including activating cancer-killing immune cells, producing immune-boosting signals, and better targeting tumors for T-cell attack.
AXL can be leveraged as a therapeutic target to enhance dendritic cell function and strengthen the body’s anti-tumor immune response, the authors wrote.
According to the study, this discovery opens the door for new strategies in cancer immunotherapy, which uses the body’s own immune system to target cancer. Targeting AXL could improve treatments by boosting the immune system’s natural cancer-fighting abilities.
While the study focuses on cholesterol’s role within dendritic cells, maintaining balanced cholesterol levels is important for overall immune function and can be influenced by diet and lifestyle choices.
