Ever heard of a sneaky game tumors play to slip past our immune system? It's called adaptive immune resistance. One trick tumors use is to make more of a protein called PD-L1, which puts the brakes on immune cells. This PD-L1 is made in a part of the cell called the endoplasmic reticulum, and it can even get packed into tiny bubbles, called extracellular vesicles, which tumor cells release into their surroundings. These vesicles can confuse and slow down our immune cells.
Here's where Sigma1 steps in. It's a unique helper protein found mostly in the endoplasmic reticulum of cancer cells. Scientists found that by blocking Sigma1 with a special drug, they could stop tumors from making PD-L1 so effectively. This means the PD-L1 and the vesicles carrying it can't work as well to trick our immune system.
In one experiment, blocking Sigma1 made PD-L1 less effective at maturing and being packaged into those sneaky vesicles. When the vesicles were released, they weren't as good at stopping our immune cells from doing their job. This suggests that by reducing the number of these tricky vesicles, we might be able to boost our immune system's fight against cancer.
So, is Sigma1 a key player in this hiding game? It seems like it might be. By understanding this, scientists could find new ways to help our immune system fight cancer.
