Immune scavenger cells: Good guys or bad guys?
The immune system is our main defense against foreign invaders (bacteria and viruses) and also against mutant cells that develop into cancer. Some of the first immune responders to these threats are scavenger cells called macrophages that destroy targets by internalizing and degrading them.
But macrophages can be tricked. When they are continually activated in a chronic disease like cancer, they can be “instructed” by cancer cells to perform functions that benefit the growing tumor instead of destroying it.
Recently, William Stallcup, Ph.D., professor at Sanford Burnham Prebys Medical Discovery Institute (SBP) published a study in Trends in Cell and Molecular Biology describing one way that cancer cells transform macrophages from tumor fighters into tumor helpers.
“We found that a protein called NG2 on macrophages is important for the ability of these scavengers to exit from blood vessels and migrate into tumors,” explains Stallcup. “When we knocked out NG2 on macrophages in mice, instead of allowing mouse brain tumors to grow faster (in the absence of the scavenging macrophages), the tumors actually grew much more slowly. This was somewhat surprising since we expect macrophages to help fight cancer.”
“It turns out that tumor cells can modify macrophage function, making them produce factors that stimulate the formation of tumor-nourishing blood vessels, says Pilar Cejudo Martin, Ph.D., a postdoc in Stallcup’s lab and first author of the paper. “By knocking out NG2, we blocked macrophage entry into tumors so that there were fewer macrophages for the tumors to use to their own advantage. So due to poor blood vessel development, tumor growth was slowed.”
So does this mean that blocking NG2 could be a general means of improving treatment of diseases involving chronic macrophage recruitment?
“It depends,” says Stallcup. “When we used a mouse model of multiple sclerosis (MS) to show that knockout of NG2 impaired macrophage entry into the damaged spinal cord, we found that recovery was hindered. That’s because macrophages are needed to produce factors that stimulate production of the cells responsible for damage repair.
“So while blocking macrophage NG2 might be useful for cancer therapy, it looks like this approach would be counter-productive for treating MS. Even though macrophages seem like attractive targets for therapy, they have such a large bag of tricks that we will probably have to deal with blocking their effects on a case-by-case basis,” adds Stallcup.
Read the paper here.