Figure 4
Figure 4. Prolonged ibrutinib therapy decreases levels of inhibitory molecules on T cells and B-CLL cells. Expression levels of PD-1 (A), CD160 (B), and CD244 (C) on ex vivo CD8+ T cells at baseline and during the course of ibrutinib treatment in patient samples (n = 7). (D-F) Pearson correlations shown between the ex vivo proliferative capacity of CTL019 cells and the expression levels of PD-1 (D), CD160 (E), and CD244 (F). Inhibitory molecule levels on baseline CLL patient (n = 8) CD8+ T cells after anti-CD19 CAR gene transfer are depicted as a fold change in expression over a biological standard. (G) Proportion of IFN-γ-producing untransduced, CTL019, or PD-1-expressing CTL019 cells generated from healthy subjects and incubated for 6 hours with the indicated stimuli. (H) Proliferative capacity (assessed at day 6) of carboxyfluorescein succinimidyl ester (CFSE)–labeled healthy donor CTL019 cells (n = 3) after PD-1 overexpression and coculture with the indicated tumor targets. (I) Expression levels of CD200 on B-CLL cells in CLL patients (n = 8) at baseline, after 1 cycle (C1), and after 5 to 11 cycles (C5-11) of oral ibrutinib therapy. Each colored circle represents an individual patient. Significant differences in expression levels as determined by 2-tailed Student t test are depicted as *P < .05, **P < .01, and ***P < .001. n.s., not statistically significant.

Prolonged ibrutinib therapy decreases levels of inhibitory molecules on T cells and B-CLL cells. Expression levels of PD-1 (A), CD160 (B), and CD244 (C) on ex vivo CD8+ T cells at baseline and during the course of ibrutinib treatment in patient samples (n = 7). (D-F) Pearson correlations shown between the ex vivo proliferative capacity of CTL019 cells and the expression levels of PD-1 (D), CD160 (E), and CD244 (F). Inhibitory molecule levels on baseline CLL patient (n = 8) CD8+ T cells after anti-CD19 CAR gene transfer are depicted as a fold change in expression over a biological standard. (G) Proportion of IFN-γ-producing untransduced, CTL019, or PD-1-expressing CTL019 cells generated from healthy subjects and incubated for 6 hours with the indicated stimuli. (H) Proliferative capacity (assessed at day 6) of carboxyfluorescein succinimidyl ester (CFSE)–labeled healthy donor CTL019 cells (n = 3) after PD-1 overexpression and coculture with the indicated tumor targets. (I) Expression levels of CD200 on B-CLL cells in CLL patients (n = 8) at baseline, after 1 cycle (C1), and after 5 to 11 cycles (C5-11) of oral ibrutinib therapy. Each colored circle represents an individual patient. Significant differences in expression levels as determined by 2-tailed Student t test are depicted as *P < .05, **P < .01, and ***P < .001. n.s., not statistically significant.

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