Fig. 7: Soquelitinib inhibits T cell exhaustion process in vitro. | npj Drug Discovery

Fig. 7: Soquelitinib inhibits T cell exhaustion process in vitro.

From: Synthesis and characterization of soquelitinib a selective ITK inhibitor that modulates tumor immunity

Fig. 7

a Schematic displaying the experimental design for evaluating the effect of soquelitinib on OT-1 T cell exhaustion process (Top). Soquelitinib inhibits the expression of several markers associated with T cell exhaustion in a dose-dependent manner. Representative histogram overlays of indicated exhaustion marker expression in CD8 + Va2+ T cells are shown at day 7 (Middle). Graph of two exhaustion markers, lymphocyte activation protein three (LAG3) and T cell immunoreceptor with Ig and ITIM domains (TIGIT) is shown (Bottom). b Schematic describing the experimental design for evaluating the effect of soquelitinib in restoring T cell function of the exhausted cells in vitro (Top). Soquelitinib dose-dependently (up to 1 μM) restores the potential functions of OT-1 CD8 T cells as indicated by increased production of granzyme B and IFNγ production following the 4 days treatment period. Representative histograms of granzyme B and IFNγ- from OT-1 T cells treated with indicated concentration of soquelitinib or DMSO control are shown (Middle). Graph of granzyme B and IFNγ-producing OT-1 T cells is shown (Bottom). c Soquelitinib inhibits the expression of several markers associated with T cell exhaustion in human CD4 + T cells. Graph of three exhaustion markers, LAG3, TIGIT, and PD1 is shown. Graphs were drawn using Graphpad Prism. Histograms and dot plots were drawn using Flowjo. Schematics were drawn using Biorender. OVA ovalbumin, APC antigen presenting cell, MFI mean fluorescence intensity, SQL soquelitinib. Data are from two separate experiments.

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