Cancer progression involves an interaction between the tumor cells and microenvironment around them, and multiple myeloma is emblematic of the impact of cancer microenvironment on tumor cells, what is the role of bone marrow microenvironment in multiple myeloma development, and how can it be influenced to prevent perhaps multiple myeloma development in the first place? And consequently, is it possible to somehow manipulate microenvironment around the cancer cells with therapeutic goals? So you have raised one of the most important question in understanding the biology of myeloma, and therapy of myeloma. And this is not a new concept. So there has been a concept about “seed in the soil”. So to explain it simply, cancer is the seed. Dr. Nikhil Munshi, MD.: But it needs the right soil for it to grow and progress. And same way myeloma cell is the seed, the bone marrow, microenvironment is the soil, the soil provides the right milieu, the right food for myeloma to grow. That's literally what happens in the lab, we have shown that myeloma cells can survive much better and grow much faster, when they are in presence of the microenvironment cells. On the other hand, for therapeutic purpose, we need to try and kill myeloma cells, we are doing all doing it. Dr. Nikhil Munshi, MD.: But equally important may be to poison the soil. So the seed does not grow. And we have now begun to have drugs for last That does both effects the myeloma cells, but also changes the microenvironment in a way that it does not support myeloma growth, that it does not support myeloma cell survival. In the presence of other treatment. We know that the microenvironment bone marrow protects myeloma cell from our drugs. So now our drugs take away the protective ability of microenvironment, and are able to kill the tumor cells much better. This has been observed with the proteasome inhibitor, by affecting the microenvironment interactions and the cytokines in the microenvironment. It happens with more immunomodulatory drugs. And it we observe it with a lot of other newer drugs, antibodies and other treatments that we are beginning to utilize. And finally, one component of the bone marrow microenvironment is the immune microenvironment. And as we will discuss more in a minute, those factors, those immune cells are actually the most critical component that we can harness to a better therapeutic efficacy.