Figure 7.
Figure 7. PTCLs rely on TCR signaling resulting from TCR–CD1d interaction for engraftment and survival. (a) Cells from PTCLs were cultured in vitro in the presence or absence of increasing concentrations of CsA (or equal concentrations of excipient ethanol, as control vehicle). Data are shown as mean ± SD of one TCRαβ-expressing PTCL in quadruplicate and are representative of four independent experiments performed with four different PTCLs. P-value was determined by two-way ANOVA test. (b) Mice were transferred with 106 PTCL cells, then left untreated (n = 5 mice) or injected i.p. daily with 20 mg/kg of CsA (n = 5 mice) for 2 wk starting from day 21 after transfer (i.e., when abdomen enlargement was clinically detectable). Transfer experiments conducted with three different PTCLs provided similar results. (c) Survival curves of WT and Cd1d−/− mice (n = 7) transferred with 106 TCRαβ-expressing PTCL cells. All mice alive at day 100 were sacrificed and showed absence of macroscopic lymphoma development. Experiments were conducted with four different PTCLs with similar results. (d) Survival curves of WT and Cd1d−/− mice (n = 5) transferred with 2 × 106 TL cells. Experiments were conducted with two different TLs with similar results. P-value was determined by log-rank test and was not significant. (e) Survival curves of WT mice transferred with 106 TCRαβ-expressing PTCL cells and injected twice a week by i.p. route with 15 mg/kg of either IgG1 isotype control (n = 8 mice) or blocking CD1d mAb from day 1 (n = 8 mice) and until mice were considered moribund and euthanized. Transfer experiments conducted with three different PTCLs provided similar results. (f) Survival curves of WT mice transferred with 106 TCRαβ-expressing PTCL cells and injected twice a week by i.p. route with 15 mg/kg of either IgG1 control isotype (n = 8 mice) or blocking CD1d mAb from day 21 (n = 8 mice; i.e., when abdomen enlargement was clinically detectable) and until mice were considered moribund and euthanized. Transfer experiments conducted with three different PTCLs provided similar results. P-values in b–f were determined by log-rank test.

PTCLs rely on TCR signaling resulting from TCR–CD1d interaction for engraftment and survival. (a) Cells from PTCLs were cultured in vitro in the presence or absence of increasing concentrations of CsA (or equal concentrations of excipient ethanol, as control vehicle). Data are shown as mean ± SD of one TCRαβ-expressing PTCL in quadruplicate and are representative of four independent experiments performed with four different PTCLs. P-value was determined by two-way ANOVA test. (b) Mice were transferred with 106 PTCL cells, then left untreated (n = 5 mice) or injected i.p. daily with 20 mg/kg of CsA (n = 5 mice) for 2 wk starting from day 21 after transfer (i.e., when abdomen enlargement was clinically detectable). Transfer experiments conducted with three different PTCLs provided similar results. (c) Survival curves of WT and Cd1d−/− mice (n = 7) transferred with 106 TCRαβ-expressing PTCL cells. All mice alive at day 100 were sacrificed and showed absence of macroscopic lymphoma development. Experiments were conducted with four different PTCLs with similar results. (d) Survival curves of WT and Cd1d−/− mice (n = 5) transferred with 2 × 106 TL cells. Experiments were conducted with two different TLs with similar results. P-value was determined by log-rank test and was not significant. (e) Survival curves of WT mice transferred with 106 TCRαβ-expressing PTCL cells and injected twice a week by i.p. route with 15 mg/kg of either IgG1 isotype control (n = 8 mice) or blocking CD1d mAb from day 1 (n = 8 mice) and until mice were considered moribund and euthanized. Transfer experiments conducted with three different PTCLs provided similar results. (f) Survival curves of WT mice transferred with 106 TCRαβ-expressing PTCL cells and injected twice a week by i.p. route with 15 mg/kg of either IgG1 control isotype (n = 8 mice) or blocking CD1d mAb from day 21 (n = 8 mice; i.e., when abdomen enlargement was clinically detectable) and until mice were considered moribund and euthanized. Transfer experiments conducted with three different PTCLs provided similar results. P-values in b–f were determined by log-rank test.

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