Skip to main content
. 2021 Dec 1;131(23):e151347. doi: 10.1172/JCI151347

Figure 6. Pharmacological depletion of the ER reverses E2-dependent melanoma tumor growth.

Figure 6

(A–C) Growth of B16F10 (0.5 × 105) (n = 9), YuMM5.2 (5 × 105) (n = 6), and BPD6 (5 × 105) (n = 5) tumors in ovariectomized C57BL/6J mice supplemented with placebo or E2 and cotreated with the ERα antagonist fulvestrant (ful). (D) Quantification of the ratio of M1/M2 macrophages isolated from BPD6 tumors in B. (E–G) Quantification of M1 macrophages (MHCIIhiCD206–), CD8+GZMB+ T cells and CD8+PD-1+ T cells in YuMM5.2 tumors from C (n = 4). (H) Individual volumes of BPD6 tumors implanted into ovariectomized mice treated with placebo or E2 following cotreatment with fulvestrant and ICB (α–PD-1 plus α-CTLA4), either alone or in combination. Vehicle plus IgG (E2 + Veh; n = 10; red); fulvestrant plus IgG (E2 + ful + ICB; n = 15; blue); vehicle plus ICB (E2 + ICB; n = 15; black); and fulvestrant plus ICB (E2 + ful; n = 15; brown). Black arrow indicates the start of the ICB treatment regimen. (I) Tumor volumes of BPD6 measured at day 12 after inoculation. (J) Individual volumes of B16F10 tumors implanted into ovariectomized C57BL6/J mice supplemented with placebo or E2 and cotreated with fulvestrant along with ICB (α–PD-1). Vehicle plus IgG (n = 9, red); fulvestrant plus IgG (n = 8, blue); vehicle plus ICB (n = 9, black); and fulvestrant plus ICB (n = 10 brown). Black arrow indicates the start of the α–PD-1 treatment regimen. (K and L) B16F10 tumor volumes measured on day 16 (all 4 groups) and day 22 (E2 plus fulvestrant vs. E2 plus fulvestrant plus α–PD-1 groups) after inoculation. (M) Median overall survival of all patients treated with immunotherapy (pembrolizumab or nivolumab alone, or in combination with ipilimumab) from the Gide et al. data set (32), with high or low E2-downregulated gene signatures derived from CD68+ cells in the scRNA-Seq experiments. Data in A– C are representative of 2 individual experiments. Data are expressed as the mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001, by 2-way ANOVA (A–C), 1-way ANOVA followed by Bonferroni’s multiple-correction test (E–G, I, and K), Student’s t test (D and L), and log-rank test (M).