Figure 6. IL15-mediated stimulation with immune checkpoint blockade improves the response to imatinib.

(A) Kit^V558Δ/+ mice were treated with IL15SA three times over the course of 9 days and given imatinib daily for 7 days. Controls received PBS for 9 days and vehicle or imatinib from days 0 to 7. (B) Tumor weights of Kit^V558Δ/+ GIST treated as described in (A) (n=5–6 mice/group, repeated twice). Flow cytometry of tumors was performed to determine: (C) Frequency of T_EM, T_CM, and T_N among intratumoral CD8⁺ T cells; and (D) Median fluorescence intensity (MFI) and representative histogram of p-AKT⁺ or p-mTOR⁺ CD8⁺ T cells in tumors from Kit^V558Δ/+ mice (n=5 mice/group, repeated twice). (E) Kit^V558Δ/+ mice were treated with IM (imatinib), IM + depleting anti-CD8 (−CD8), IM + IL15SA, or IM + IL15SA + −CD8 and assessed for tumor weight and frequency of CD8⁺ T cells among CD45⁺ cells, as assessed by flow cytometry (4–5 mice/group). (F) Kit^V558Δ/+ mice were treated with IM, IM + aPD1 (anti-PD1), IM + IL15SA, or IM + IL15SA + aPD1 for 4 weeks and assessed for tumor weight (5 mice/group, pooled from two independent experiments). Flow cytometry was used to assess these mice for (G) CD8⁺ T-cell subsets and (H) frequency of Ki67⁺ and Granzyme B⁺ cells among CD8⁺ T. Line indicates median; *, p < 0.05.