Figure 6.

Effect of Src, JAK and mTOR kinase inhibitors on T cell exhaustion induced by prolonged treatment with CD19-TCB. PBMCs co-cultured with SU-DHL-8 tumors cell were stimulated by CD19-TCB in the presence of 100 nM dasatinib (Src inhibitor), 100 nM sirolimus (mTOR inhibitor) or 100 nM ruxolitinib (JAK inhibitor) for 5 days. Cells from technical duplicates were pooled and the expression of PD1, TIM3 and LAG3 on CD4⁺ and CD8⁺ was measured by flow cytometry. (A) Histogram plots showing the effects of 100 nM dasatinib (Srci), 100 nM sirolimus (mTORi) and 100 nM ruxolitinib (JAKi) on the expression of PD1, TIM3 and LAG3 induced by 10 nM CD19-TCB for n=3 donors. (B) The dose-response curves show the effect of kinase inhibitors on PD1, TIM3 and LAG3 expression on CD4⁺ and CD8⁺ T cells, means of n=3 donors±SD with *p≤0.05 by one-way analysis of variance (Kruskal-Wallis test). LAG3, lymphocyte-activation gene 3; PBMCs, peripheral blood mononuclear cells; PD1, programmed cell death protein-1; TCB, T cell bispecific antibody; TIM3, T cell immunoglobulin and mucin-domain 3.