Abstract
Although the role of estrogen in solid cancers has been widely investigated, its effect in hematologic malignancies including multiple myeloma (MM) is not known. Here, we utilized a syngeneic mouse model of MM to address this question. In this model, treatment with 17β-estradiol significantly promoted progression of the disease. This effect has not been attributed to the direct effect of estrogen on MM cells but rather was mediated through estrogen-induced alterations in tumor microenvironment. In MM bone marrow, myeloid-derived suppressor cells (MDSCs) represent one of the major cellular populations. 17β-estradiol did not promote expansion and accumulation of MDSCs. However, it significantly increased their ability to suppress T cells proliferation. Thus, these data demonstrated that estrogen promotes progression of MM by enhancing an immunosuppressive function of the bone marrow MDSCs.