CXCR2 blockade promotes MM control in murine MM models. Vk12653 murine MM cell lines were injected into recipients for different in vivo tumor models (see “Materials and methods” for full details). We used the following models: the NDMM model (tumor cell injection without irradiation, n = 40 from 2 experiments), the RRMM model (tumor cell injection followed by total body lethal irradiation, 1000 cGy, and syngeneic [autologous] stem cell transplant, n = 40 from 2 experiments), the CD8⁺ T-cell depletion mouse model (tumor cell injection without irradiation, n = 40 from 1 experiment), and the NSG mouse model (tumor cell injection without irradiation, n = 30 from 1 experiment). Progression of MM was confirmed by weekly serum protein electrophoresis measurement of the monoclonal protein (M-spike) to albumin ratio in the NDMM model. In the RRMM model, the mice were classified as MM-relapsed or MM-remission based on the M-spike to albumin ratio. Recipient BM was harvested and stained with appropriate antibodies. Results were analyzed via flow cytometry. (A) Quantification of frequency and number of CXCR2⁺ neutrophil clusters from the samples of CBM (no tumor injection), MTB, and HTB, the latter 2 based on serum protein electrophoresis measurements. Cells gated from CD11b⁺Ly6G⁺Ly6C^– population. (B) Quantitation of M-spike development, and survival curve in the NDMM model. (C) UMAP representation of immune cells (excluding macrophages and neutrophils) observed in various experimental arms in the NDMM model. Cell type distribution highlighted below UMAP to show changes in cell kinetics upon treatment. (D) Concatenated mature neutrophils show distinct developmental stages observed in humans with little variance among experimental conditions: EIN represent $x¯$ = 22.39%, σ = 2.06%, LIN represent $x¯$ = 22.87%, σ = 1.36%, EMN represent $x¯$ = 28.23%, σ = 0.66%, LMN represent $x¯$ = 26.5%, σ = 2.96%. Neutrophils were scored with the same signatures as Figure 2. (E) Quantitation of M-spike development, and survival curve in T-cell depletion mouse model. (F) Quantitation of M-spike development, and survival curve in NSG mouse model. (G) Quantitation of M-spike development, survival curve, and CD8⁺ T-cell cytokine expression of IFN-γ and TNF-α. Data represent mean ± standard error of the mean. The 2-way analysis of variance was used to analyze statistical significance among tumor growth in different groups. Survival data are presented as percent survival (log-rank Mantel-Cox test). ∗P < .05; ∗∗P < .01; ∗∗∗P < .001. CBM, control bone marrow; EIN, early immature neutrophils; EMN, early mature neutrophils; HTB, high tumor burden bone marrow; LIN, late immature neutrophils; LMN, late mature neutrophils; MTB, moderate tumor burden bone marrow; ns, not significant; PBS, phosphate buffered saline; TNF-α, tumor necrosis factor-α.