Fig. 6

Inhibition of Chokα preferentially eliminated CD4 + PD1^high cells from the tumors in mAITL preclinical model and from AITL patient biopsies in vitro. A Schematic representation of the CDP-choline pathway with the step inhibited by MN58b indicated. (C) Effect of Chokα inhibitor MN58b treatment on mAITL lymphoma cells in vitro. The survival of the CD4 + T cells (B) and the % of residual CD4 + PD1^high tumoral cells (C) are indicated. Percentages are normalized to corresponding vehicle-treated cells set at 100%. D Splenic lymphoma cells from plck-GAPDH mice were injected intravenously into recipient NSG mice (n = 10), which were treated with vehicle (n = 5) or MN58b (n = 5) by IP injection. Mice were sacrificed at 60 days post-transplant. E Spleen size and weight are shown for the indicated treatment groups at sacrifice. CD4 + PD1^high (F) and GC B (G) cell counts in the spleen for the indicated treatment groups at sacrifice. Data are summarized in the histograms (mean ± SD, Vehicle: n = 5, MN58b: n = 5; *p < 0.05, **p < 0.01, ***p < 0.001). H Effect of Chokα inhibitor (MN58b) treatment (72 h) on the CD4 + T cell survival of LN biopsies of 7 different AITL patients compared to CD4 + T cells in PBMCs from healthy donors as control. Percentages are normalized to corresponding vehicle-treated (DMSO) control cells set at 100%. I FACS analysis of percentage of CD4 + PD1^high cells on total CD4 + T cells of LN biopsies of 6 different AITL patient biopsies after 72 h of MN58b or Vehicle (DMSO) treatment. A representative FACS plot is shown for n = 6 and individual AITL donors are represented in a histogram