DC-derived IL-10– and CSF-1R–dependent macrophages promote myeloma relapse after SCT. MM-bearing recipients were transplanted as previously described with BM+T grafts from B6 donors. (A-B) MM-bearing recipients were transplanted with IL-10–deficient (IL-10^−/−; red) or WT (blue) grafts and CD8⁺ T cell phenotype was assessed in the BM 4 weeks after SCT. (A) Representative FACS plot and number of activated (CD69⁺DNAM-1⁺) and (B) exhausted (DNAM-1⁻TIGIT⁺TIM-3⁺PD-1⁺) CD8⁺ T cells (n = 6 from 1 experiment). (C) Survival of MM-bearing recipients transplanted with BM grafts from donors either deficient in CD11c-derived IL-10 (CD11cCre⁺ × IL-10^fl/fl; red) or littermate controls (CD11cCre⁻ × IL-10^fl/fl; blue) and sorted WT T cells (n = 13 combined from 2 experiments). (D) Survival of MM-bearing recipients treated with 500 μg cIg (gray) or anti-IL-10R (green) twice a week from week 2 to week 6 after SCT (n = 10 combined from 2 experiments). (E) MM-bearing and MM-free recipients were transplanted with BM+T from CSF-1R-mApple reporter mice. CSF-1R expression on macrophages (CD64⁺Mϕ) was determined 6 weeks after SCT in the BM (n = 3-5 from 1 experiment). (F) M-band and survival of MM-bearing recipients treated with 400 μg cIg (gray) or anti-CSF-1R (M279; light blue) twice a week from week 2 to week 6 post-SCT (n = 10 combined from 2 experiments). Survival was analyzed using a log-rank test, and M-bands were modeled as described. Data represent mean ± SEM and a Mann-Whitney U test was used for numerical values. *P < .05.