Estrogen drives accumulation of myelomonocytic (M-MDSC) and granulocytic (G-MDSC) MDSCs and increases the immunosuppressive potential of G-MDSCs. Estrogen.

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Estrogen drives accumulation of myelomonocytic (M-MDSC) and granulocytic (G-MDSC) MDSCs and increases the immunosuppressive potential of G-MDSCs. Estrogen drives accumulation of myelomonocytic (M-MDSC) and granulocytic (G-MDSC) MDSCs and increases the immunosuppressive potential of G-MDSCs. A, Intraperitoneal (i.p.) LLC lung tumor progression in oöphorectomized vs. sham-treated WT mice (left) or subcutaneous (s.c.) LLC growth in WT mice treated with vehicle (Vh) vs. E2 (right; 5 mice/group in both cases). B, Flank A7C11 breast tumor growth in oöphorectomized WT mice treated with vehicle (Vh) vs. E2 (5 mice/group). C, 5 × 105 B16.F10 cells (ATCC) were injected i.v. into mice (n = 5/group). Upon injection, mice were treated with vehicle (0.1% EtOH) or E2 (10 μmol/L) in drinking water. After 15 days, mice were euthanized and the number of lung metastases per mm2 was determined by hematoxylin and eosin staining. Representative images of lung metastases are also shown. D and E, Expression and quantification of M-MDSCs (Ly6ChiLy6G−) and G-MDSCs (Ly6C+Ly6G+) in the spleen of ID8-Defb29/Vegfa peritoneal tumor-bearing mice. F and G, Expression and quantification of M-MDSCs (Ly6ChiLy6G−) and G-MDSCs (Ly6C+Ly6G+) in the peritoneal cavity of ID8-Defb29/Vegfa peritoneal tumor-bearing mice. H, Flank A7C11 breast tumor growth in oöphorectomized mice treated with vehicle (Vh) vs. E2 and receiving 250 μg of anti-Gr1 (RB6-8C5; BioXCell) vs. control isotype antibodies every other day, starting at day 2 after tumor challenge (5 mice/group). I, Dilution of Cell Trace Violet in labeled T cells activated with anti-CD3/CD28 beads cocultured with varying ratios of M- and G-MDSCs isolated from ID8-Defb29/Vegfa tumors. *, P < 0.05; **, P < 0.01. Nikolaos Svoronos et al. Cancer Discov 2017;7:72-85 ©2017 by American Association for Cancer Research