Fig. 1: Combining adrenergic receptor (β-AR) blockade with doxorubicin results in increased survival of mice with EL4 lymphoma and is associated with changes in MDSC frequency.

A, B The EL4 tumor was given i.v. to mice followed by propranolol (daily; i.p.; 1 mg/kg), or doxorubicin (day 7; i.v.; 4 mg/kg), or both. The mice were treated with (A) Isotype (**p = 0.0026) or (B) anti-Gr1 depleting antibody (twice weekly; i.p.; 1 mg/kg). Two-sided Mantel-Cox log rank test. Frequency of (C) CD11b⁺Ly6C⁺Ly6G^- (M-MDSC) (*p = 0.0264; **p = 0.0055; ***p = 0.0002) and (D) CD11b⁺Ly6C⁺Ly6G⁺ (PMN-MDSC) (**p = 0.0467; **p = 0.0012; **p = 0.0075) in bone marrow of mice treated as in (A). Apoptosis rate in (E) M-MDSCs (*p = 0.0110; **p = 0.0025; **p = 0.0025) and (F) PMN-MDSCs (**p = 0.0026; **p = 0.0028; **p = 0.0062) from (A) measured by Annexin V staining (apoptotic cell: Aqua⁺ Annexin V⁺). Activated levels of caspase 3 determined by CaspGLOW™ Caspase-3 staining on (G) M-MDSCs (*p = 0.0195; **p = 0.0065) and (H) PMN-MDSCs (*p = 0.0493; **p = 0.0014; **p = 0.0068) from mice treated as in (A). Activated levels of caspase 8 determined by CaspGLOW™ Caspase-8 staining on (I) M-MDSCs (*p = 0.0114; *p = 0.0169; **p = 0.0016) and (J) PMN-MDSCs (**p = 0.0026; ***p = 0.002; ***p = 0.003) from mice treated as in (A). In (C−J) data presented as mean ± SEM. Pool of two independent experiments with n = 5 mice per group. Survival of EL4 tumor bearing mice in WT vs. β2AR^-/- mice treated with doxorubicin (day 7; i.v.; 4 mg/kg) and treated with (K) Isotype (**p = 0.0019) or (L) anti-Gr1 depleting antibody (twice weekly; i.p.; 1 mg/kg). Two-sided Mantel-Cox log rank test. M Survival of EL4 tumor bearing recipients in WT, β2-AR^-/- and the conditional β2-AR^fl/fl LysM^Cre myelomonocytic population knockouts. WT compared to β2-AR^fl/fl-LysM^Cre mice treated with doxorubicin (day 7; i.v.; 4 mg/kg) (**p = 0.0064). Two-sided Mantel-Cox log rank test. Source data containing independent experiments raw data are provided as a Source Data file.