Tuesday, July 14, 2015

Natural Killers and Lymphoma

Fascinating research out of Germany: Lymphoma cells seem to have the ability to switch off the body's immune system if certain immune cells get too close to the lymphoma cells. Understanding how and why that happens might provide some new targets for researchers.

The original research appears (or will appear) in the European Journal of Immunology; unfortunately, I can't find the article, or even a title. All I have to go on is a piece from Medical News Today. But it's fascinating enough that I want to comment on it here, even without seeing the full original article.

The research described focuses on particular cells called Natural Killer cells (known as NK cells). NK cells are a type of white blood cell, and an important part of our immune system. When things are working normally, the NK cells will attack viruses and even new tumor cells. They are very special cells -- unlike many white blood cells that work when they are given a signal by an antigen, NK cells can recognize invaders all on their own. Imagine a dog that needs its owner to give a command before it attacks an invader versus a dog that can figure out who belongs and who doesn't.

NK cells kill  by releasing toxic chemicals. Cool video about it here.

What the researchers in this study found was that NK cells are shut down when they get too close to lymphoma cells. (Here's where lack of access to the original article might be a problem -- no idea if the research focuses on particular types of lymphoma cells or not).

When NK cells were placed near the lymphoma cells in live mice, they shut down. When they were then repositioned away from the lymphoma cells, they started working again within a few hours.

So what it is about lymphoma cells that shuts down the NK cells and keeps them from doing their jobs (that is, from killing the lymphoma cells)?

There are two possible things that happen.

The first is that the lymphoma cells release something called IL-10, or Interleukin-10. IL-10's job is anti-inflammatory. When the body is invaded (say, during an infection), IL-10's job is to make sure the response isn't so overwhelming that the immune system starts to damage healthy cells as well as the invader. When things go wrong, this means IL-10 is getting too good at its job, and not letting the immune system go after the bad guys. IL-10 in the lymphoma cells seems to do its job too well, and block NK cells.

The second way is that the lymphoma cells deactivate the NK cells' NKG2D ligands. The ligands are the things on the surface of the cell that let them attach to invaders and hold them down while they poison them to death. Watch that video above and you'll see the ligands in action. When they don't work, the NK cells can't hang on to the bad guys, and they get away.

The interesting part of this comes from what we do with all of this knowledge. If we follow the path we have been following, that means we develop treatments that target IL-10 and whatever deactivates the ligands. Once they are shut down, the NK cells can do their job and clean up cancer cells before they get out of hand.

But there's another possibility -- removing the NK cells and activating them, and then returning them to the body. This skips that step that shuts them down, and lets them get to work.

(I'm not sure how that will work, exactly, but it sounds like a kind of lymphoma vaccine.)

So, this information isn't going to lead to a treatment any time soon. But it does give us another path to follow.

More importantly, it gives us another piece of that big puzzle -- all of the small things that need to be dealt with in order for the Big Thing to be taken care of. As much as we'd like to have a single treatment that can wipe out Follicular Lymphoma (or any type of cancer), we're learning more and more that it's going to take at least a few different treatments to target different steps that keep cancer cells from being killed off.

The important thing, the hopeful thing, is that we're learning more and more.


Anonymous said...


I think it might be this article published from Springer: "Critical role of the NKG2D receptor for NK cell-mediated control and immune escape of B-cell lymphoma", Ralph Mocikat et all., European Journal of Immunology, article first published online: 7 JUL 2015


Greetings from Germany

Lymphomaniac said...

That's the one! Thank you. Hope all is well in Germany.