Progressive immunosuppression from immature to mature neutrophils. (A) Fluorescence-activated cell sorting of the 3 neutrophil subsets from BM samples of MM patients (n = 10) and HAs (n = 4) was performed to culture each subset with autologous T cells previously stimulated with CD3/CD28 antibodies and labeled with violet proliferation dye (VPD). After a 4-day incubation, VPD intensity was measured on total T cells. (B) Total BM samples vs BM samples depleted of each neutrophil subset (ie, BM without CD11b⁻CD13^−/loCD16⁻, BM without CD11b⁺CD13^−/loCD16⁻, and BM w/o CD11b⁺CD13⁺CD16⁺) from MM patients (n = 10) were treated with 30 nM of a BCMA×CD3-bispecific antibody and left in culture for 24 hours. (C) Significant decrease in T-cell proliferation when these were stimulated in the presence of mature neutrophils from MM patients (0.5-fold; P = .016), but not the immature or intermediate subsets from MM patients or HAs. (D) Cytotoxic potential of T cells engaged by a BCMA×CD3-bispecific antibody progressively increased with the depletion of immature, intermediate, and mature neutrophils (two-, three-, and fourfold, respectively; P ≤ .03). Bars represent the mean and lines the standard error of the mean. Statistical significance was evaluated using the Student t test for proliferation analysis and the Kruskal-Wallis test for the immunosuppression assay. *P < .05, **P < .01, ***P < .001.