RT Journal Article SR Electronic T1 Myeloid-derived suppressor cell subsets drive glioblastoma growth in a sex-specific manner JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.02.19.954552 DO 10.1101/2020.02.19.954552 A1 Defne Bayik A1 Yadi Zhou A1 Chihyun Park A1 Changjin Hong A1 Daniel Vail A1 Daniel J. Silver A1 Adam J. Lauko A1 Gustavo A. Roversi A1 Dionysios C. Watson A1 Alice Lo A1 Tyler J. Alban A1 Mary McGraw A1 Mia D. Sorensen A1 Matthew M. Grabowski A1 Balint Otvos A1 Michael A. Vogelbaum A1 Craig M. Horbinski A1 Bjarne Winther Kristensen A1 Ahmad M. Khalil A1 Tae Hyun Hwang A1 Manmeet S. Ahluwalia A1 Feixiong Cheng A1 Justin D. Lathia YR 2020 UL http://biorxiv.org/content/early/2020/02/20/2020.02.19.954552.abstract AB Myeloid-derived suppressor cells (MDSCs) that block anti-tumor immunity are elevated in glioblastoma (GBM) patients. However, the distinct contribution of monocytic (mMDSC) versus granulocytic (gMDSC) subsets has yet to be determined. We observed that mMDSCs were enriched in the male tumor microenvironment, while gMDSCs were elevated in the circulation of female GBM models. Depletion of peripheral gMDSCs extended the survival only in female mice. Using gene expression signatures coupled with network medicine analysis, we demonstrated in pre-clinical models that mMDSCs could be targeted with anti-proliferative agents in males, whereas gMDSC function in females could be inhibited by IL-1β blockade. Analysis of patient data confirmed that proliferating mMDSCs were the predominant population in male tumors, and that a high gMDSC/IL-1β gene signature correlated with poor prognosis of female patients. These findings demonstrate that MDSC subsets differentially drive immune suppression in a sex-specific manner and can be leveraged for therapeutic intervention in GBM.Statement of Significance Sexual dimorphism at the level of MDSC subset prevalence, localization and gene expression profile comprises a therapeutic opportunity. Our results indicate that chemotherapy can be used to target mMDSC in males, while IL-1 pathway inhibitors can provide benefit to females through blockade of gMDSC function.