Fig 2: IL-6 does not promote intrinsic B-ALL chemoresistance.a A flow cytometry plot showing IL-6R expression on the surface of leukemic cells in vitro. Histograms for IL-6R and isotype control-stained cells are overlaid. b A graph showing IL-6R expression in the bone marrow of leukemia-bearing mice pre- and post-doxorubicin (DOX) treatment. Data were quantified by flow cytometry. mCherry+ leukemia cells were used to distinguish stromal and leukemia cells. Median APC intensity from IL-6R stained cells minus isotype control-stained cells was calculated. Data from 2 independent experiments are shown, and represented as mean ± SEM. n = 6 per cohort, except n = 7 for both IL-6 KO-D2 post-doxorubicin stroma and IL-6 KO-D2 post-doxorubicin leukemia samples. ****p < 0.0001 by Ordinary one-way ANOVA test. c A dose–response curve showing leukemic cell viability in response to doxorubicin treatment in the presence or absence of IL-6 and/or sIL-6R. Viable cells were counted by flow cytometry 48 h after the addition of doxorubicin. Data from 4 independent experiments are shown, and represented as mean ± SEM. d A dose–response curve showing leukemic cell viability in the presence or absence of cytokines previously observed to be regulated by IL-6. Cells were treated as in (c) with the indicated cytokines. e A dose–response curve showing leukemic cell viability of cells co-cultured with bone marrow stromal cells (BMSC) from WT or IL-6 KO mice in response to doxorubicin treatment as in (c). f A graph showing p-STAT3 levels in the bone marrow of leukemia-bearing WT and IL-6 KO mice. There were no significant statistical comparisons between corresponding WT and IL-6 KO samples. Data are shown as in (b), from 2 independent experiments, and represented as mean ± SEM. n = 7 per cohort, except n = 6 for both IL-6 KO-D2 post-doxorubicin stroma and IL-6 KO-D2 post-doxorubicin leukemia samples. *p = 0.011, ****p < 0.0001 by Ordinary one-way ANOVA test. D2 = Day 2. Source data are provided as a ‘Source data’ file.

Fig 3: Therapeutic IL-6 inhibition enhances the efficacy of doxorubicin treatment.a A Kaplan–Meier survival curve of B-ALL-bearing mice. n = 15 for both doxorubicin (DOX) + Isotype and doxorubicin + αIL-6R treated, n = 10 for untreated, and n = 5 for αIL-6R only treated mice. **p = 0.0062 by Log-rank (Mantel-Cox) test. b A graph showing leukemia burden in WT mice treated with doxorubicin and either an IL-6R blocking antibody or isotype control. Tumor burden was monitored by bioluminescence imaging. n = 7 for doxorubicin + Isotype, n = 9 for doxorubicin + αIL-6R treated mice. ***p = 0.0002 by two-tailed Mann–Whitney test. c A graph showing PDAC tumor burden in WT mice treated with doxorubicin and either an IL-6R blocking antibody or isotype control. n = 10 for Isotype only, n = 15 for αIL-6R only, n = 19 for doxorubicin + Isotype, and n = 22 for doxorubicin + αIL-6R. Data from 4 independent experiments. **p < 0.035, ***p < 0.005, ****p < 0.0001. d A graph showing PDAC tumor burden on day 18 for individual animals within the indicated treatment groups. Shown are the individual biological replicates from (c). ****p < 0.0001. e A graph showing PDAC tumor burden in WT and IL-6 KO mice treated with doxorubicin or untreated. n = 10 per cohort, except n = 19 for WT-doxorubicin only. Data from 1 independent experiment. *p < 0.05, **p < 0.035, ****p < 0.0001. f A graph showing PDAC tumor burden on day 18 for individual animals within the indicated treatment groups. Shown are the individual biological replicates from (e). ***p = 0.0003, ****p < 0.0001. g A graph showing PDAC tumor burden of secondary transplants (5 days after doxorubicin treatment) into IL-6 KO mice that had already received a primary PDAC transplant and were treated with doxorubicin or untreated. n = 10 per cohort. *p < 0.05, **p < 0.035. h A graph showing PDAC tumor burden on day 8 for individual animals within the indicated treatment groups. Shown are the individual biological replicates from (g). **p = 0.0039. Two-tailed Mann–Whitney tests were used to compare groups in panels (c–h), and data are represented as mean ± SEM. Boxplots show the median as the center lines, upper and lower quartiles as box limits, and whiskers represent maximum and minimum values. D2 = Day 2, D8 = Day 8. Source data are provided as a ‘Source data’ file.