BETA - What is the bone marrow microenvironment (BMME)? Is it the same thing as the immune microenvironment? What makes up the microenvironment?

The cells of bone marrow microenvironment all interact to create a niche that allows myeloma cells to grow, survive and resist treatment. Researchers are actively developing therapies that target key components of the bone marrow microenvironment. This Health Tree University course aims at building a better understanding of the microenvironment. Let's start from first talking a little bit of what the bone marrow microenvironment is. So, as we know, multiple myeloma cells come from aberrant plasma cells. And normal plasma cells are made in the bone marrow. So, the bone marrow is the hematopoietic tissue that usually is found inside all the major bones in the spine, in the hip, in the ribs. And this is kind of like a dynamic tissue where there are lots of different cellular components. So, there are different types of immune cells. That's why sometimes we talk about immune microenvironment for myeloma. So, there are like T cells, B cells, myeloid cells, macrophages. There are like different types of cells that stay there. There is also like practically a matrix, a net of like fibers and proteins that are there to support the growth of different types of cells. And then there are other cell types like endothelial cells like blood vessels, osteoblasts and osteoclasts that are like practically cells and help to make or destroy bones. So, the bone microenvironment is really the place where normal hematopoiesis, or normal blood cell production occurs. And myeloma cells usually stay there. So, when we talk about multiple myeloma, by definition, we need to have a certain percentage of plasma cells in the bone marrow that is higher than normal. And what the myeloma cells do, they can kind of like reshape the bone marrow microenvironment in a way that helps them grow or prevent immune, antitumoral immunity, for instance. This environment can change and can change because of different factors. One is really the myeloma cells. The other one is treatment. Age can also affect some of these components. But overall, when we talk about tumor microenvironment, most of the time we are referring to the bone marrow microenvironment, the immune microenvironment. Saying so, sometimes the myeloma can change and become a little bit more aggressive and go to different places. When we talk about extra medullary myeloma, this is something that sometimes people, especially after multiple lines of therapy, can get. The myeloma cells can kind of detach and become independent from the bone marrow microenvironments and practically go to a different place and grow there. So they are still able to change their environment, but they're not in the bone marrow anymore. And that's why technically it's better in this case to talk about tumor microenvironment, because it's not really in the bone marrow. And finally, there is also a condition called plasma cell leukemia that is not as common as myeloma, and this myeloma can be a primary diagnosis, an individual patient can present with that diagnosis, or it can be an evolution again of the myeloma. And in this case, the myeloma cells practically lose a lot of adhesion marker or retaining marker to the bone marrow, and they can go in the peripheral blood behaving like a leukemia. So in this case, there are like all these differences and changes in the bone marrow and the actually tumor microenvironment that are important for the survival of the myeloma cells and that important to study, because as you can imagine, if we know how to change the microenvironment, we might be able to better kill the cells, the myeloma cells. The immune microenvironment technically is the same as the bone marrow microenvironment. And when we say that term, we're basically referring to the immune cells that surround the cancer cells. So as you know, the bone marrow is our factory of producing blood cells, whether it's the red blood cells or the white blood cells or the platelets. For the case of multiple myeloma, multiple myeloma, as a lot of people know, it grows within the bone marrow. And it's definitely always surrounded by other normal cells or the healthy cells that the bone marrow is producing as part of its normal function. So anything that's surrounding the myeloma cells, that's what we call the immune microenvironment. So it's the ecosystem that I guess would be a good way to describe the ecosystem that myeloma grows in. And that can be the white blood cells, the platelets, the stem cells, the red blood cells, all within the bone marrow. And the reason why we talk about it a lot these days is that we know that myeloma alone is not the only thing that's causing all the problems that patients face. Myeloma does have a lot of genetic abnormalities that are making it malignant and aggressive. But we do know that with more studies that there is a lot of interaction happening between those myeloma cells in the bone marrow and the immune microenvironment surrounding it. And we know that there are cases where the microenvironment is more permissive. That's what we call it. We call it more permissive for myeloma to grow faster or in a more aggressive way. And that's where immunotherapy actually comes in and plays a role. We know that with immunotherapy we're able to help those immune cells surrounding myeloma in terms of attacking myeloma, controlling it, killing myeloma. But also at the same time, because different people have different immune microenvironments, that's why we also see a difference in response. Some immune systems are a little bit better than others. Some are weaker, some are stronger. And that's why we see a huge difference in outcomes as well, even when we use immunotherapy. To learn more about the immune status of the bone marrow microenvironment and how that is measured, watch the Health Tree University video on this topic in our Immunotherapy Basics course.