作者
Defne Bayik, Yadi Zhou, Chihyun Park, Changjin Hong, Daniel Vail, Daniel J Silver, Adam Lauko, Gustavo Roversi, Dionysios C Watson, Alice Lo, Tyler J Alban, Mary McGraw, Mia Sorensen, Matthew M Grabowski, Balint Otvos, Michael A Vogelbaum, Craig Horbinski, Bjarne Winther Kristensen, Ahmad M Khalil, Tae Hyun Hwang, Manmeet S Ahluwalia, Feixiong Cheng, Justin D Lathia
发表日期
2020/8/1
期刊
Cancer discovery
卷号
10
期号
8
页码范围
1210-1225
出版商
American Association for Cancer Research
简介
Myeloid-derived suppressor cells (MDSC) that block antitumor immunity are elevated in glioblastoma (GBM) patient blood and tumors. However, the distinct contributions of monocytic (mMDSC) versus granulocytic (gMDSC) subsets have yet to be determined. In mouse models of GBM, we observed that mMDSCs were enriched in the male tumors, whereas gMDSCs were elevated in the blood of females. Depletion of gMDSCs extended survival only in female mice. Using gene-expression signatures coupled with network medicine analysis, we demonstrated in preclinical models that mMDSCs could be targeted with antiproliferative agents in males, whereas gMDSC function could be inhibited by IL1β blockade in females. Analysis of patient data confirmed that proliferating mMDSCs were predominant in male tumors and that a high gMDSC/IL1β gene signature correlated with poor prognosis in …
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D Bayik, Y Zhou, C Park, C Hong, D Vail, DJ Silver… - Cancer discovery, 2020