Figure 6 from Extracellular Vesicle Secretion by Leukemia Cells In Vivo Promotes CLL Progression by Hampering Antitumor T-cell Responses

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sEVs are crucial for CLL development by impairing the antitumor immune response in vivo.A, Generation of a new TCL1-RAB27DKO mouse model. B, Detection of the human TCL1 transgene and Rab27b excision in gDNA of C57BL/6, TCL1, and TCL1-RAB27DKO mice. C, Immunoblot analysis of RAB27A and RAB27B proteins in the same mice. D, Percentage of CD5+CD19+ CLL cells in the PB of TCL1 (n = 35) or TCL1-RAB27DKO (n = 12) mice over time. E, Survival of mice from D and RAB27DKO mice (n = 10). F, Quantity of proteins recovered from LME-sEVs (n = 18) or LME-sEVsTCL1-RAB27DKO (n = 11) normalized per gram of spleen. G, PCA based on differentially expressed proteins (DEP) between LME-sEVsTCL1-RAB27DKO and LME-sEVs with FDR <0.05 and log2FC >1. H, Volcano plot showing DEP. I, 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). J, Percentage of CD5+CD19+ CLL cells in the blood of C57BL/6 mice injected according to I (n = 16 per condition). Four different clones for each genotype were injected into 4 mice each. K, 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). L, Percentage of CD5+CD19+ CLL cells in the PB of mice injected according to K (n = 6 per group) at days 14 and 21 (left) and in the spleen of the same mice at day 21. M, 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+ T cells treated ex vivo with HCME- (blue arrows) or LME-sEVs (red arrows). N, Percentage of CD5+CD19+ CLL cells at day 10 in the PB of mice injected according to panel M (n = 4 per group). O, Survival of mice from M (n = 4 per group). *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001 (unpaired Student t test for F, L, and N two-way ANOVA followed by the Bonferroni multiple comparison test for D and J, log-rank test for E and O). Data are mean with SEM.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.