Biology of Immune Regulation in Multiple Myeloma

Multiple myeloma (MM) is a malignancy of plasma cells (PCs) which accumulate in the bone marrow (BM), thus, leading to anemia, bone lesions, hypercalcemia, renal impairment and immune dysfunction. T regulatory (Treg) cells maintain immune homeostasis in healthy individuals by patrolling unwanted immune responses. Whereas in cancer patients, these cells are uncontrollably expanded, thereby, inhibiting the host anti-tumor responses. Majorly this work is focused to understand the role of Treg cells, including CD4 Treg cells and CD8 Treg cells in rendering the immune impairments in MM patients. This study clearly showed that both CD4 and CD8 Treg cells were functionally suppressive and increased in MM patients. These findings were confirmed by using different methods, including flow cytometry, functional and molecular studies (RT-PCR and western blot). Clinical significance of this study was CD4 Treg cells were found to be increased in patients with shorter time to progression, hypercalcemia, lower normal PC counts ( 5%) and IgA myeloma subtype. From these findings, Treg cells could be considered as one of the evasion mechanisms of myeloma cells from host immune responses.