Abstract Summary: Svoronos and colleagues observed estrogen receptor alpha–positive cells in the tumor stroma of patients with ovarian cancer that appeared to be independent of both the tumor's estrogen receptor status and tumor type. These cells were identified as immunosuppressive myeloid-derived suppressor cells (MDSC) and could be targeted by antiestrogen therapy, thereby leading to the hypothesis that endocrine therapy when combined with immunotherapy may provide a potential therapeutic benefit by helping to reduce immunosuppressive MDSCs. Cancer Discov; 7(1); 17–9. ©2017 AACR. See related article by Svoronos et al., 72.