Cancer and autoimmune disease are two sides of the same coin
Autoimmune diseases, such as diabetes, arthritis, and inflammatory bowel disease, are caused by overactivation of the immune response
while cancer cells downregulate the immune response in order to promote their own growth
One attractive therapeutic target, lymphotoxin β receptor (LTβR) on the cell surface, is central to both processes
but its detailed signaling mechanisms have remained unclear, making it difficult to target the pathway
Now, researchers have identified a way to alter the strength of LTβR-mediated signaling
Using drugs to lower the cholesterol levels in the plasma membrane
they showed that the lipid content of the cell membrane affects LTβR-dependent signaling and LTβR internalization
Depleting membrane cholesterol caused increased LTβR signaling through the well-known canonical NF-κB signaling pathway
suggesting that cholesterol depletion could be used to augment LTβR-based therapies for cancer
and cholesterol levels may also affect the outcome of treatment for autoimmune disease
Although further mechanistic details remain to be uncovered this discovery could help improve immune-targeting therapies,
improving the chances of success in cases where traditional treatment has failed
Banach-Orlowska, et al. “Cholesterol restricts lymphotoxin β receptor-triggered NF-κB signaling.” Cell Communication and Signaling (2019).