Estrogen promotes multiple myeloma through enhancing the immunosuppressive activity of MDSC.

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.