Figure 3.
Depletion of phagocytic myeloid subsets results in decreased tumor burden in vivo and prolongs survival. (A) Schematic diagram depicting the dosing schedule for clodlip treatment to deplete myeloid cells in mice with established transplanted LN3 T-ALL. (B) Representative images from the indicated organs of control or clodlip-treated mice after establishment of T-ALL burden. Immunostaining for T-ALL cells (CD45.2; green), F4/80 (red), CD11c (magenta), and DAPI (blue) is shown. Scale bars, 100 μm. (C) Quantification of the frequency of T-ALL cells in the blood and numbers of T-ALL cells in the spleen, BM, thymus, and inguinal LNs in control and clodlip-treated mice. Bars depict means + standard error of the mean (SEM) of cumulative data from 5 to 8 experiments, each with a distinct color-coded primary T-ALL; circles represent individual mice. (D) Quantification of the weights of spleens and livers from control and clodlip-treated mice from the same experiments as in (C). Bars show means + SEM from 5 independent experiments, each with a distinct color-coded primary T-ALL; circles represent individual mice. (E) Graph displays cumulative survival of control and clodlip-treated mice from 2 independent experiments, each with a different primary LN3 T-ALL, using the treatment regimen in (A). The Kaplan-Meier survival curves were normalized to the first day of death in each experiment. (F) Quantification of viable T-ALL cells, isolated from the spleens of LN3 T-ALL–transplanted mice 6 or 7 days after culture in the presence or absence of enriched myeloid cells from the spleens of tumor-bearing or tumor-free mice. Results were normalized to the viability of T-ALL cells cocultured with tumor-associated myeloid cells within each experiment (red line). Bars depict means + SEM of cumulative data from 3 experiments, each with a distinct color-coded primary T-ALL; circles represent the mean of 2 or 3 replicate wells per experiment. (G) Schematic diagram depicting the dosing schedule to deplete myeloid cells prior to T-ALL engraftment in congenic recipients. (H) Graph displays cumulative survival of control and clodlip-treated mice from 3 independent experiments, each with a different primary LN3 T-ALL. The Kaplan-Meier survival curves were normalized to the first day of death in each experiment. *P < .05, **P < .01, ***P < .001, unpaired Student t test (C-D), log-rank test (E,H), repeated measures one-way ANOVA with the Bonferroni correction (F).

Depletion of phagocytic myeloid subsets results in decreased tumor burden in vivo and prolongs survival. (A) Schematic diagram depicting the dosing schedule for clodlip treatment to deplete myeloid cells in mice with established transplanted LN3 T-ALL. (B) Representative images from the indicated organs of control or clodlip-treated mice after establishment of T-ALL burden. Immunostaining for T-ALL cells (CD45.2; green), F4/80 (red), CD11c (magenta), and DAPI (blue) is shown. Scale bars, 100 μm. (C) Quantification of the frequency of T-ALL cells in the blood and numbers of T-ALL cells in the spleen, BM, thymus, and inguinal LNs in control and clodlip-treated mice. Bars depict means + standard error of the mean (SEM) of cumulative data from 5 to 8 experiments, each with a distinct color-coded primary T-ALL; circles represent individual mice. (D) Quantification of the weights of spleens and livers from control and clodlip-treated mice from the same experiments as in (C). Bars show means + SEM from 5 independent experiments, each with a distinct color-coded primary T-ALL; circles represent individual mice. (E) Graph displays cumulative survival of control and clodlip-treated mice from 2 independent experiments, each with a different primary LN3 T-ALL, using the treatment regimen in (A). The Kaplan-Meier survival curves were normalized to the first day of death in each experiment. (F) Quantification of viable T-ALL cells, isolated from the spleens of LN3 T-ALL–transplanted mice 6 or 7 days after culture in the presence or absence of enriched myeloid cells from the spleens of tumor-bearing or tumor-free mice. Results were normalized to the viability of T-ALL cells cocultured with tumor-associated myeloid cells within each experiment (red line). Bars depict means + SEM of cumulative data from 3 experiments, each with a distinct color-coded primary T-ALL; circles represent the mean of 2 or 3 replicate wells per experiment. (G) Schematic diagram depicting the dosing schedule to deplete myeloid cells prior to T-ALL engraftment in congenic recipients. (H) Graph displays cumulative survival of control and clodlip-treated mice from 3 independent experiments, each with a different primary LN3 T-ALL. The Kaplan-Meier survival curves were normalized to the first day of death in each experiment. *P < .05, **P < .01, ***P < .001, unpaired Student t test (C-D), log-rank test (E,H), repeated measures one-way ANOVA with the Bonferroni correction (F).

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