Understanding the Immune System

I've been going back into my files, looking at some of the older things that I set aside to look at later. Well, it's later now. Here's an interesting piece published about a month ago on OncLive.

It's an interview with Dr. Stephen Ansell from the Mayo Clinic in Minnesota, who talks about the challenges of understanding the immune system, and how greater understanding might lead to better lymphoma treatments. The interview is based on a presentation he made at the SOHO (Society of Hematologic Oncology) meeting in September.

As Dr. Ansell points out, the immune system is very complex. There are several different immune cells, and they serve different functions, targeting different invaders, working in sequence or together to fight infection. While we know the basics of how those cells work, we're only really just beginning to understand how to harness their power to treat cancer. You can see their promise when you think about the two types of treatments that get Lymphoma experts most excited right now -- CAR-T (which changes immune cells in a lab so they can detect cancer cells) and bispecifics (which bring immune cells into close contact with cancer cells). 

So when you consider that those treatments have been very effective, but not completely effective, one question to ask is, when they stop working, is it because of some issue with our not understanding completely how immune cells work? In other words, if CAR-T works well and gets a Complete Response, but then stops working, what changed? In theory, T cells have a memory -- once they encounter their target, they will remember it for the next time it shows up. So what happens with refractory CAR-T (when it worked but then stopped working)? Do they stop remembering? Did they change in some way? Those are the kinds of questions that need to be answered.

And, of course, there are questions that go beyond CAR-T and bispecifics, which target CD 19 and CD20 proteins on cancer cells. Another type of treatment being developed uses a different kind of immune cell called a macrophage, even more powerful than T cells. Macrophages can target yet another protein, CD47.

Then there is the question of treatment sequencing. If certain treatments are given after others stop working, do they have a negative effect on the immune system, in ways that prevent other immune-cell-based treatments from working effectively? In other words, if chemo messes with the immune system, will that make CAR-T less effective later on, because it involves the immune cells that need to be changed to find the cancer cells?

And what about treatment combinations? Would adding, say, Rituxan to another immunotherapy create problems? There's always the danger of increased side effects with combining treatments. But will one of those side effects be lessening the effectiveness of the immune cells that are being used to treat the cancer?

I find it all very fascinating. I always thought, way back in school, that the immune system was interesting. I thought it was strange that we had this kind of second blood system, the lymphatic system, that no one ever talked about. Now here I am with Lymphoma. Isn't life funny?

But I do find it all fascinating, and I'm glad that lots of researchers do, too.  I'm sure we'll see lots of improvements to current treatments, and maybe some new treatments, coming out of all of this research in the next few years.