Figure 6 from Extracellular Vesicle Secretion by Leukemia Cells <i>In Vivo</i> Promotes CLL Progression by Hampering Antitumor T-cell Responses
<p>sEVs are crucial for CLL development by impairing the antitumor immune response <i>in vivo.</i><b>A,</b> Generation of a new TCL1-RAB27DKO mouse model. <b>B,</b> Detection of the human <i>TCL1</i> transgene and Rab27b excision in gDNA of C57BL...
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2025
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| Sumario: | <p>sEVs are crucial for CLL development by impairing the antitumor immune response <i>in vivo.</i><b>A,</b> Generation of a new TCL1-RAB27DKO mouse model. <b>B,</b> Detection of the human <i>TCL1</i> transgene and Rab27b excision in gDNA of C57BL/6, TCL1, and TCL1-RAB27DKO mice. <b>C,</b> Immunoblot analysis of RAB27A and RAB27B proteins in the same mice. <b>D,</b> Percentage of CD5<sup>+</sup>CD19<sup>+</sup> CLL cells in the PB of TCL1 (<i>n</i> = 35) or TCL1-RAB27DKO (<i>n</i> = 12) mice over time. <b>E,</b> Survival of mice from <b>D</b> and RAB27DKO mice (<i>n</i> = 10). <b>F,</b> Quantity of proteins recovered from LME-sEVs (<i>n</i> = 18) or LME-sEVs<sub>TCL1-RAB27DKO</sub> (<i>n</i> = 11) normalized per gram of spleen. <b>G,</b> PCA based on differentially expressed proteins (DEP) between LME-sEVs<sub>TCL1-RAB27DKO</sub> and LME-sEVs with FDR <0.05 and log<sub>2</sub>FC >1. <b>H,</b> Volcano plot showing DEP. <b>I,</b> Injection scheme of CLL cells competent (TCL1, red arrows) or deficient in sEV release (TCL1-RAB27DKO, green arrows) into C57BL/6 mice, with or without LME-sEVs (violet arrows). <b>J,</b> Percentage of CD5<sup>+</sup>CD19<sup>+</sup> CLL cells in the blood of C57BL/6 mice injected according to <b>I</b> (<i>n</i> = 16 per condition). Four different clones for each genotype were injected into 4 mice each. <b>K,</b> Injection scheme of CLL cells deficient in sEV release (TCL1-RAB27DKO, green arrows) into C57BL/6 mice, treated with α-CD8 blocking or isotype-control Abs (violet arrows). <b>L,</b> Percentage of CD5<sup>+</sup>CD19<sup>+</sup> CLL cells in the PB of mice injected according to <b>K</b> (<i>n</i> = 6 per group) at days 14 and 21 (left) and in the spleen of the same mice at day 21. <b>M,</b> Injection scheme of CLL cells deficient in sEV release (TCL1-RAB27DKO, green arrows) into C57BL/6 mice, together with α-CD8 blocking Ab (violet arrows) and followed by injection of activated CD8<sup>+</sup> T cells treated <i>ex vivo</i> with HCME- (blue arrows) or LME-sEVs (red arrows). <b>N,</b> Percentage of CD5<sup>+</sup>CD19<sup>+</sup> CLL cells at day 10 in the PB of mice injected according to panel <b>M</b> (<i>n</i> = 4 per group). <b>O,</b> Survival of mice from <b>M</b> (<i>n</i> = 4 per group). *, <i>P</i> < 0.05; **, <i>P</i> < 0.01; ***, <i>P</i> < 0.001; ****, <i>P</i> < 0.0001 (unpaired Student <i>t</i> test for <b>F</b>, <b>L</b>, and <b>N</b> two-way ANOVA followed by the Bonferroni multiple comparison test for <b>D</b> and <b>J</b>, log-rank test for <b>E</b> and <b>O</b>). Data are mean with SEM.</p> |
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