Figure 4. Treatment with SRI31277 restores MM sensitivity to BTZ in OB-Runx2^−/− mice.

A,Schematic diagram of the tumor injection and treatment schedule for mice used in experiments in B-O. 5-week-old OB-Runx2^−/− and OB-Runx2^+/+ mice were i.v. injected with 5TGM1-Luc MM cells (down arrow) 1 week before treatment with PBS, BTZ, SRI31277, or BTZ+SRI31277 (left up arrow) for 4 weeks. Blood and BM were collected at study end (right up arrow) for all analyses (n=5–9 mice/group). B, Quantification of serum IgG2bκ concentration in mice after treatment, measured by ELISA in duplicate (n=5–9 mice/group). C-E, BM cells harvested after treatment were analyzed by flow cytometry for the percentage of CD138⁺ MM cells among all B220⁺ B cells (C) and the percentage of Ki-67⁺ MM cells (D) and cleaved caspase-3-positive MM cells (E) among the CD138⁺ cells (n=5 mice/group). F, Percentage of MDSCs (Gr1⁺ CD11b^hi) in the BM cell population. G-I, Relative expression of iNOS (G), arginase 1 (H), and IL-10 (I) in total MDSCs (Gr1⁺ CD11b^hi). J, Gating strategy for identifying CD8⁺ T cells and CD8⁺ T cells expressing exhaustion and activation markers in the BM cell population. K, Percentage of CD8⁺ T cells detected among all CD3⁺ T cells (CD3⁺CD8⁺) in the BM. L-O, Percentage of CD8⁺ T cells in the BM expressing PD-1 (L), TIM-3 (M), granzyme B (N), and IFN-γ (O). Data are presented as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.005, ****P < 0.001. ns, not significant.