Fig. 5: Soquelitinib inhibits tumor growth and enhances cytolytic capacity of tumor-infiltrating T cells.
a Soquelitinib elicits anti-tumor activity in a range of murine syngeneic tumor models. Mice with established tumors indicated here were treated with vehicle/control chow or solution-formulated soquelitinib, 30 mg/kg (CT26 and EL4), 10 mg/kg (RENCA and B16F10-OVA) or soquelitinib chow, 130 mg/kg (A20) daily for 7–8 days (all tumors except A20) or for 13 days (A20). Tumor measurements were performed 2–3 days after last dosing. Results are representative of at least two independent experiments. n = 5–8/group. b Soquelitinib treatment increases intratumoral CD8 infiltration in the CT26 tumor model. Percentage of CD8+ TILs was determined by flow cytometry from isolated CT26 tumors treated with either vehicle or soquelitinib for 8 days. c Soquelitinib-treated animals showed increased production of inflammatory cytokines in tumor infiltrating lymphocytes (TILs) from the CT26 tumors. IFNγ- and/ or tumor necrosis factor (TNF)- producing T cells were assessed by intracellular cytokine staining after restimulation ex vivo with PMA+ionomycin for 4 h. (n = 8 per group). d Soquelitinib increases expression of CD107a on CD8 TILs. TILs purified from individual CT26 tumors were stimulated ex vivo with the plate-bound anti-CD3 and soluble anti-CD28 for 4 h. Degranulation of CD8+ TILs was measured by flow cytometry. Quantification of CD107a+ cells is expressed as the absolute numbers of CD107a + CD8 + T cells per mm3 of tumors. Representative of two independent experiments is shown. Graphs were created using Graphpad Prism. NS not significant, *p ≤ 0.05, and **p ≤ 0.005. Data displayed as means ± SEM. SQL soquelitinib.
