Tumor Microenvironment in POD24

Well, the winners of the Social Health Awards were announced yesterday, and unfortunately I did not win either of the awards that I was a finalist for. That's fine -- it really was an honor to make it to the finals, and the winners of all 10 awards do really amazing work. So I'm happy for them. And I thank you all again for all of your support, during the awards nominations and over the last 14+ years. 

I'll keep doing what I do.

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Very cool research from the Journal of Hematology and Oncology, getting us one step closer (we hope) to figuring out the mystery of POD24.

A little background first. POD24 (sometimes called EFS24) stands for Progression of Disease within 24 Months. It's the idea that, for Follicular Lymphoma patients who have recieved successful immunochemotherpay (like R-CHOP or B +R), if the disease returns within 24 months, their outcomes are worse than other FL patients. Some research published earlier this year suggests that the media 5 year survival for FL patients is about 90%, but for POD24 patients, it's about 50%.

Figuring out POD24 is a big priority in the Lymphoma community. There are so many unanswered questions about FL in general, and even more for POD24. There have been lots of attempts to find biomarkers for POD24 -- something in the cells or the genes -- that can help doctors identify POD24 patients early on and treat the disease aggressively.  Or, even better, create new treatments that will act on those biomarkers in some way.

The research published in JHO is the latest attempt at finding biomarkers. The article is called "Revealing the evolution of the tumor immune microenvironment in follicular lymphoma patients progressing within 24 months using single-cell imaging mass cytometry." It involves some pretty heavy science, but I think it's fascinating.

A lot of cancer research lately focuses on the "tumor microenvironment." Basically, this is research that works on the assumption that cancer cells don't just survive because of what is in the cell themselves. Instead, they rely on things happening on their micro-environment -- the area that is right around the cell. There must be something nearby that is protecting the cell in some way.

This research looks at the ways that the body's immune system protects FL cells. The body does produce abnormal cells from time to time, and typically, the immune system recognizes them as problematic, and takes care of them before they can become an issue. But sometimes, something happens that allows them to slip past the immune system and become a problem. That's what might happen with POD24, according to this research -- the immune stystem not only allows the FL cells to keep growing, but might play an active role in protecting the cells.

Our immune system is kind of amazing. It has lots of different layers, so certain cells kind of float around and take care of simple problems. If they can't handle a problem, a different set of immune cells comes in to help, and sends out signals to even more immune cells. And if they can't handle it, even more powerful immune cells come in to help. 

(Of course, there are downsides to all of this. Our body reacts to all of this immune activity in ways that can be problematic, too. Cytokine Release Syndrome, for example, is a potentially serious side effect of CAR-T therapy that happens when the immune system is over-activated.)

 As for the research in the article, the researchers found that the tumor microenvironment -- the area that surrounds the cancer cells -- created a barrier to the FL cells, so immune cells could not get to them. They did this by recruiting certain immune cells (regulatory T cells) and macrophages (very powerful immune cells). It is especially important that the cancer cells can control the regulatory T cells, since these are the immune cells that control (or regulate) how the body is going to respond to an immune problem. 

The researchers looked especially at proteins that were on the immune cells that were causing the problems, and identified which cells had certain proteins or were missing certain proteins. (If you're interested in the specifics, the article says:

"More FL-cells in the peri-follicular regions suffered CD8⁺T cells attacks under simultaneous protection of regulatory T cells (Tregs) and/or macrophages compared with that in the follicles irrespective of POD24. During POD24, increased CD163⁻ macrophages with PD-1 ligand upregulation and decreased CD8⁺T cells with upregulated LAG-3 expression around FL-cells were observed in the follicles.")

The details matter to researchers, because those are the potential targets for any new treatments. Immunotherapy is all about using the body's immune system to treat cancer, either by changing the immune cells to recognize cancer cells, or by changing cancer cells so the immune system can control them. The researchers in the article hope that identifying those specific cells, and the specific features on those cells, can eventually lead to treatments that can target them.   

And that's the other really important thing to remember about this research: it's still just taking place in a laboratory, looking at cells and not at whole, complete people. This is very early research. In fact, it is published as a letter to the editor, rather than a peer-reviewed article. In other words, the research hasn't been reviewed by other researchers yet to validate it.

So while it's valuable, it will be a long time before it leads to any new treatments.

Still, I think it's pretty fascinating research, and it tells us something about how researchers are thinking about Follicular Lymphoma, and especially about how to handle the POD24 problem. It really is a priority for researchers, and even though it only affects about 20% of FL patients, it's nice to hear that those who are having the most difficulty are getting the attention.

And any new knowledge about FL and what makes it incurable is bound to help all of us.