Effects of anti-CD38 agents on Breg-like CLL cells, Tregs, T helper, and cTLs in a CLL PDX model. A short-term PDX-CLL clinical trial concept mouse model was developed via injecting (IV) PBMCs isolated from a patient with CLL (clinical characteristics in Table 1, Pt. 22) into NSG mice. After 24 hours, mice were treated with vehicle (V), daratumumab (D, 20 µg/mL loading dose followed by 10 µg/mL), or kuromanin (K, 20 µg/mL) by IV tail vein injection on postimplantation days 2, 5, and 8. On day 9, mice were sacrificed, with the spleen and blood harvested, followed by human immune cell analysis carried out showing the absolute number of CD19⁺CD5⁺ CLL cells (A); Breg-like CLL cells (CD19⁺CD5⁺CD24⁺CD38⁺) (B); Tregs (CD4⁺CD25⁺FoxP3⁺) cells (C); CD38⁺Tregs (CD4⁺CD25⁺CD127^lo/FoxP3 gated cells) (D); T-helper cells Th1, Th2, and Th17 subsets (E); CD8⁺ cTLs (F); PD1⁺CD38^hiCD8⁺ cTLs (G); Granzyme B⁺CD8⁺ cTLs (H); and LAMP1⁺CD8⁺ cTLs (I) were probed and gated for using human antibodies in mouse splenocytes cells. Absolute cell counts for Bregs, Tregs, Th1, Th2, Th17, and cTLs were also determined and are shown in supplemental Table 2. Contour plots are representative and compiled data are presented as mean ± SEM with individual data points overlaid. Each experiment was performed at least twice in duplicate. *P < .05; **P < .001.