BETA - How can understanding changes in the bone marrow (immune) microenvironment improve myeloma outcomes?

Welcome to this Health Tree University lesson, where we'll dive into one of the most fascinating and important topics in blood cancer research. The bone marrow microenvironment, or BMME, think of it as the neighborhood where blood-forming stem cells live, grow, and thrive. This environment isn't just a passive backdrop, it's alive with activity made up of a mix of supportive cells like fibroblasts, macrophages, endothelial cells, and fat cells, all working together and communicating through signaling molecules like cytokines. But what happens when this neighborhood is disrupted, when cancer like multiple myeloma moves in and begins to reshape the environment to its own advantage? In this lesson, we'll explore how the BMME changes in the presence of myeloma, how it supports cancer growth, and why understanding these changes can open the door to smarter, more targeted treatments. How can understanding changes in the bone marrow microenvironment improve myeloma outcomes? I have an active lab that studies myeloma and myeloma genomics, which is the study of the DNA of the myeloma cells in patients. And we also study the immune microenvironment, which is the surrounding cells around the myeloma, where it grows in the bone marrow and sometimes outside of the bone marrow. And indeed, over time, our focus has changed from looking just at the tumor cells to looking at more holistically the tumor cells in the context of the surrounding. And we are learning that there are cellular structures in the surrounding that are important. There are proteins that are secreted by those cellular structures that are important. And there are stromal units that also make up the bone marrow that are important. So to explain more, just like a bird would build its nest, the myeloma cell tries to create a nest for itself in the bone marrow by secreting proteins that would make the environment more conducive, like a nest for itself. And in doing so, it activates cells that are already there in the bone marrow. These can be bone forming cells like osteoblasts and bone remodeling cells like osteoclasts. It also recruits the support of what are called stromal cells. And these cells actually support the myeloma cells' growth over time. You had mentioned how the myeloma environment changes over time. So the change can happen either in these two compartments, that is, the bone remodeling cells or the supporting stromal cells for the myeloma cells. And in fact, stromal cells have been found to make the myeloma cells more resistant to chemotherapy over time. So they almost protect the cells from treatment. The bone marrow stroma is composed of several types of stromal cells, including fibroblasts, macrophages, adipocytes, bone marrow, mesenchymal stromal cells, endothelial cells and myeloid cells. These cells play a crucial role in the process of blood cell formation. Another very, very important component of the environment, which we are learning more and more about as the technology improves and as our understanding of the interaction of the immune system and myeloma improves, is that the immune cells in the microenvironment are also used by myeloma cells to evade detection, almost like stealthy predators. They have found ways to cloak themselves and evade detection so they can grow. And we are now developing drugs that will overcome that and actually help our own immune system to recognize the tumor better and to kill it better. We have T cells in the environment, natural killer cells and other immune cells that recognize myeloma cells that also have properties of presenting the myeloma cells as antigens to the immune system. And these are very, very important. Over time, as patients age and get treated, these three aspects, the bone, the stromal cell and the immune microenvironment can all change under the pressure of the treatment. The tumors also evolve over time. So it is this symbiotic relationship between bone marrow, cellular components, as well as tumor that changes over time and under selection pressures of different treatments that we see in our patients as they go from precursor stages to newly diagnosed to relapse to even extra medullary myeloma. Environment keeps changing and myeloma also changes and we are developing drugs now to actually treat this.