How can myeloma cells evade immune surveillance?
The role of Adenosine production in suppression of immune response to Multiple Myeloma
For fighting against Multiple Myeloma, which is a cancer has tumor cells grow in bone marrow, we want to wake up our immune army. Our immune army is supposed to destroy the cancer cells, but it fails because of some suppressive commands in our body. So find out these suppressive commands and weaken them to help our immune army wake up.That's what I am studying on now.
In order to develop an efficient immunotherapy for Multiple Myeloma(MM), we need to understand whether and how the immune response recognize and control the tumor in the Bone marrow environment. We choose one possible reason which maybe responsible for this immune suppression in Multiple Myeloma --- the upregulation of adenosine(ADO) in bone marrow microenvironment. Tumors may use this mechanizm to subvert immune system. Many tumors and tumor-infiltrating cells upregulate CD39 and CD73, which leads to adenosine-mediated T suppression. Immune responses to myeloma cells are believed to take place in bone marrow, so manipulation of the immune response at that site could be important to reject tumor cells. The aim of our study is to determinate whether and how generation of adenosine from extra-cellular ATP in the bone marrow contributes to suppression of myeloma-specific immune response, and to investigate whether blocking ectonuclease activity or inhibiting ADOR on T cells could induce a myeloma specific immune response capable of rejecting the tumor. We have found that ADO/INO/AMP are higher in MM patients than normal, and MM patients have more CD39+ plasma cells which means they may have higher ability to produce ADO. We also found that some MM cell lines express a lot CD39, and these cell lines can convert ATP to AMP quickly. However, they can not convert AMP to ADO because the lack of CD73. In bone marrow, a lot of cells express CD73, like some B cells, mesenchymal stem cells and stromal cells. Adding these cells to MM cell lines can produce a lot ADO, which means this system may release high level of ADO. Then, we found if we co-culture T cells with these MM cell lines and stromal cells, as a result of upregulation of ADO, T cells are suppressed. Block the receptors on T cells, this suppression disappears. We need to repeat these experiments and add more data. As far as now, this project goes well and we need more time to collect enough data.