Fig. 2: Targeted inhibition of SF3B1 by pladienolide B prevents tumor growth and increases cytotoxic lymphocyte infiltration.
a Flow chart of mouse tumor inoculation and drug administration. ID8 cells (2 × 105) were subcutaneously injected into the left groin of C56BL/6 mice (6–8 weeks old). After three days, mice were randomized into treatment cohorts accordingly (n = 6 for each group) and given drug treatment: vehicle (10% DMSO in PBS) or pladienolide B (0.5 mg/kg, every 3 days, 6 times). After the tumors were palpable, tumor volume was evaluated every 3 days. Treatment was stopped at day 18 and tumors growth was still monitored for another 5 weeks. b Growth curve of tumor volume. c Image of transplantation tumors in vehicle group and pladienolide B group. d Line chart of body weight of mice in vehicle group and pladienolide B group. e Diagram of flow cytometry gating strategies for tumor-infiltrating immune cells. f Amount of macrophage cells per milligram tumor in vehicle group and pladienolide B group. g Amount of macrophages per milligram tumor in vehicle group and pladienolide B group. h Amount of neutrophils per milligram tumor in vehicle group and pladienolide B group. i The proportion of CD86 + F4/80 + M1 macrophages to macrophages in vehicle group and pladienolide B group. j The proportion of CD163 + F4/80 + M2 macrophages to macrophages in vehicle group and pladienolide B group. k The proportion of CD8+ cells to CD3+ cells in vehicle group and pladienolide B group. l The proportion of IFN-γ + CD8+ cells to CD8+ cells in vehicle group and pladienolide B group. m The proportion of FOXP3-CD4+ cells to CD4+ cells in vehicle group and pladienolide B group. n The proportion of FOXP3 + CD25 + CD4+ Treg cells to CD4+ cells in vehicle group and pladienolide B group. p values were determined by non-parametric t tests. *p < 0.05. **p < 0.01. ***p < 0.001.
