What is the tumor microenvironment?

What is the tumor microenvironment? The tumor microenvironment consists of all the cells besides the cancer cell in the organ system that they reside in. For myeloma specifically, it's the bone marrow microenvironment for the most part because plasma cells like to live in the bone marrow microenvironment. So you have other type of blood cells, stem cells, different immune cells, bone marrow stromal cells, bone forming and bone destroying cells. All of those cells are in that microenvironment. So it's kind of like the cancer cells neighborhood. It's going to be a little bit dependent on what tumor type you're talking about, but here we're going to talk about myeloma and for the most part we're going to talk about the bone marrow. So the bone marrow is normally where plasma cells should be living. This is the neighborhood that the plasma cells are living in. They have a variety of different neighbors who are doing different things. That includes immune cells. It includes things like the bone cells, the fat cells, cells that we call stromal cells. It also includes things that are being made by all of those cells. So different growth factors and cytokines. And all of that is feeding into the myeloma cell, in some cases allowing the myeloma cells to grow more aggressively so they can kind of hijack the normal neighborhood and turn it into something that allows them to keep growing out of control. Does the microenvironment change from time to time? It does. So that microenvironment does change from time to time. Disease burden, the kind of disease that patients have, has a role to play in this as well because the myeloma cells in higher burden, they are themselves producing chemicals and signals that influence the activity and behavior of their neighboring cells too. Are there ways to change the microenvironment? That's complicated as well. We have known for a while that the imids, the immunomodulatory drugs like linoleumide and pomelinamide certainly do have effects on the tumor microenvironment for myeloma. But it's so complicated that we aren't really sure what all these drugs are doing even though they've been around for a while. But there's a lot of interest in developing newer drugs that really do target the neighborhood. So if you can kind of clean up the neighborhood, then maybe you can get rid of those pesky myeloma cells. Is there a test to see what the microenvironment looks like and what's there? Not quite yet. There's certainly a lot of research effort going on, but at this point there's not just a test that your doctor back home in their clinic can order that's going to tell you the strength of the tumor microenvironment. Certainly my hope would be that if we're talking again in the next couple of years that that will change, but right now it's too complicated. Are there studies in myeloma right now that are looking at the microenvironment? Absolutely. There are studies looking at targeting the environment, also studies looking at how does the immune environment add to people relapsing from myeloma. How does the bone marrow microenvironment affect CAR T cell therapy? That concept is about how easy it is for CAR T cells to get to where they're going. And this is where certain types of cancer cell types are more ingrained in their neighborhood and get a bit more added protection from the microenvironment or the neighbors. So that's where that concept comes from. I think that that concept also speaks to the fact that more high risk phenotypes of myeloma like extra medullary myeloma, they have a different microenvironment because these myeloma cells are not just in the bone marrow. They can be in the soft tissue or the liver or the lymph nodes or other areas. So different microenvironments have different neighbors or key stakeholders, I guess. So susceptibility of the cancer cells can be influenced because of those interactions. So we need to understand how some myeloma cells might be able to resist that attack, that T cell attack on them. And then there are other factors, say for example in the bone marrow environment, negative signals that are being sent out that suppress the function of those CAR T cells when you put them in or suppress the function of your own unmodified T cells when you're using bispecific antibodies. So all of that's going to need to be factored into play when we're designing optimal immunotherapies for myeloma for the future. But that's work that's ongoing.