There is an entire branch of our immune system that has evolved to recognize when something is wrong inside a cell, and it revolves around a group of proteins called .
MHC-I is a little pedestal that cells use to display their proteins for immune cells called to inspect. If everything is normal and healthy, the proteins on the MHC-I pedestal won’t cause any alarm, and the cell is allowed to continue happily growing and dividing. However, if something in the cell has gone awry – whether that is viral infection, bacterial infection, or cancer – what gets displayed on the MHC-I can signal a problem. In that case, a T-cell will immediately kill the cell to nip the problem in the bud.
In a perfect world, this would work every time and our immune system could always stop cancer in its tracks. But some cancers are able to avoid detection by the immune system by not producing MHC-I at all.
A led by scientists at the NYU School of Medicine and the University of California - San Francisco showed that pancreatic cancer cells recycle and degrade MHC-I complexes so fast that there are almost none on the cell surface to signal that something is wrong.
To try to increase the amount of MHC-I present on the surface of cancerous cells, the researchers treated pancreatic cancers of mice with chloroquine, which prevents the cells from degrading MHC-I complexes. When this was combined with immunotherapy, they saw that more T-cells flooded the area around the tumor, and that this was correlated with a significant decrease in tumor size and weight. This discovery has the potential to improve treatment for cancers that were previously resistant to immunotherapy, making it a promising new strategy to combat them.