BETA - Can therapy target the bone marrow (immune) microenvironment to make it more friendly to anti-myeloma therapies?

In previous Health Tree University lesson, we learned the bone marrow immune microenvironment can affect how an individual living with myeloma responds to therapy. In this lesson, we will discuss if the bone marrow immune microenvironment can be changed to make it more friendly. The bone marrow microenvironment where the myeloma cells reside is very important for multiple myeloma cellular growth. So it is unbalanced, so there is usually a tendency towards less activation and more immunosuppression. So the lymphoid cells are not very good in killing myeloma cells. And also at the same time, there is an unbalance between destroying bone compared to making new bones. In the past 20, 30 years, we've been really, although scientific field has been working hard on trying to understand how we can change, how we can modify this bone marrow microenvironment not to fit the needs of the cancer cells, but to actually make them die quicker, for instance. And one medication, a series of medication that has been used is really are called biphosphonate. So biphosphonate are medication that were used before mainly for osteoporosis and our cells that are medication that are helpful in activating some cells called osteocytes or osteoblasts that are the type of bone cells that are in the bone marrow microenvironment that are important to make new bone matrix, new bone structures. In myeloma, usually these osteoblasts are kind of like stunned, are kind of like dormant and tired. And the osteoclasts are more active and they actually chew and keep like destroying bones if left unattended. So biphosphonate can kind of like help activate the osteoblasts to make new bones. And the way that also work, there were some initial studies that can also kind of change the microenvironment, making myeloma cells growing less. Other therapies that we know have been used for kind of changing the microenvironment are immunomodulatory drugs such as lenalidomide, pomalidomide and the new cell mod. So they practically what they do, they change, try to activate more the immune cells, the lymphoid cells. And more and more there are new data, new more like experimental studies that are showing how other medication that are not really ready to be given to patients can change a little bit all these balances in patients. So some are medication that kind of change the epigenetics. So like the DNA expression and the RNA expression of cells kind of like moving them towards the type of characteristics of the immune cells that we want. And they've been like studied in different settings, usually in animal models still to kind of see if using this medication can be helpful for changing the microenvironment and then bring it to like to patients. The immune system is a very complex set of mechanisms involving cells, other types of signals and interacting with tumor cells and normal cells and so forth. It's a highly orchestrated system. And a lot of research up to now has been very focused on T cells because T cells are the cells that kill myeloma cells. But a lot of steps go into activating T cells and keeping them in fighting shape so they can kill tumor cells, infected cells and so forth. And there's a growing appreciation that we can manipulate those other parts of the immune system to optimize T cell activity. So there's a lot of interest in probably two general areas. One is NK cells. So NK are natural killer cells, like their name implies, can kill targets such as tumor cells. And a lot of research has been gone into developing strategies that help NK cells kill tumor cells. But NK cells also play an important regulatory role in helping T cells get activated and keep keeping them fit. So a lot of NK cell directed strategies also complement T cell directed strategies. And as these newer NK therapies progress in their development, the possibility of combining them with T cell directed therapies is very exciting and very important. The other major area are in what are called myeloid cells. So myeloid cells are part of the immune system. They do a lot of different functions. They are like the garbage trucks of the immune system. They go and scavenge up dead cells and things like that. They play a very important role in presenting targets to T cells. So things like virus proteins and bacteria proteins and cancer proteins are displayed to T cells so that T cells can recognize and say, that's bad. I'm going to kill cells that have that particular target. And there are strategies to increase the activity of myeloid cells. And there are various kinds of myeloid cells I'm oversimplifying so that you can have good myeloid cells that will help T cells and to eliminate bad myeloid cells that hinder T cell activity. And it's interesting to note that one of the oldest of the novel therapies, the immunomodulatory drugs, actually have very broad effects not only on T cells and B cells, but also on NK cells and myeloid cells. So IMID drugs and now the newer drugs such as cell mods will undoubtedly have a role in helping orchestrate immune responses against myeloma.