Extended Data Fig. 5: PMN-MDSCs Infiltration Relays on IL-8 (Cxcl15) / CXCR2 Signaling Following ADT.
From: Castration-mediated IL-8 promotes myeloid infiltration and prostate cancer progression
a, PMN-MDSCs as a percentage of CD45+ cells in the TME of indicated human prostate tumors as determined by flow cytometry (n = 3 LNCaP and n = 6 PC3 tumors per group, 2 independent experiments). b, Representative H&E and immunohistochemistry (Ly6G and F4/80) sections of the indicated human prostate xenografts (repeated x3). c, Dorsal prostate transgenic NPK tumors (p = 0.0493) and d, Anterior prostate transgenic NPK tumor (p = 0.0006). Left: representative H&E and immunohistochemistry of Ly6G in transgenic NPK tamoxifen-inducible prostate tumors harvested from untreated (CS group) or ADT-treated mice (CR group). CTX (degarelix) was administrated 3 months after tamoxifen-induction, and tumors were harvest 30 days later; right: Ly6G positive counts per mm2 of tumor area as described in the methods section. e, PMN-MDSC density normalized to mg of tumor weight in transgenic NPK tamoxifen-inducible prostate tumors from mice treated as described in c-d (p = 0.0208; cells/mg; n = 4 CS & n = 3 CR tumors per group). f, Left: representative H&E and immunohistochemistry of Ly6G in non-cancerous murine prostate from castration-sensitive (CS), androgen-deprivation treated (pADT) non-tumor bearing mice, and ADT-treated mice that received testosterone repletion (pADT + T). Repeated x2; right: counts of Ly6G positive cells per field as described in the methods section. g, Representative histograms of protein expression determined by flow cytometry in PMN-MDSCs from indicated organs (repeated x2). h, Representative H&E and immunohistochemistry (Ly6G and F4/80) on CR-Myc-CaP allografts treated as indicated (repeated x3). i, Representative H&E and immunohistochemistry (Ly6G and F4/80) in PC3 tumor xenografts treated as indicated (repeated x3). H&E and IHC images are 40X magnification; scale bar=50 μm. Bar plots represent means with SEM. Unpaired two-tailed (a-e) t-tests were performed, p-values ≤ 0.0001 (****); p-values ≥ 0.05 (ns). For f, Tukey’s multiple comparisons test with a single pooled variance was performed.
