Figure 4.
Tolinapant requires an intact immune system to generate long-term tumor regressions. (A) Cytotoxic cells score in BW5147 subcutaneous tumors in vehicle and tolinapant-treated mice (log2 scale). *P < .05 (2-sided Welch t test adjusted using the Benjamini and Yekutieli method). (B) Intratumoral expression of Gzmb, Gzme, and Prf1. *P < .05, **P < .01 (adjusted P value). (C) Representative immunofluorescent images and boxplot showing quantification of CD8+ cells in tumor sections. **P < .001 (Mann-Whitney test). Tumor formalin-fixed paraffin-embedded sections were costained with fluorochrome-conjugated anti-CD8 (red) antibody and DAPI (blue). (D) Heatmap of the selected genes that are differentially expressed (adjusted P value < .05) between vehicle and tolinapant-treated BW5147 tumors, displayed as gene-wise z scores (log2 normalized expression). Selected genes were obtained from gene expression signatures associated with different pathways scored with NanoString Advanced Analysis GSA module. (E) Immunodeficient CB17 SCID mice were treated with vehicle or with 16 mg/kg tolinapant (daily oral) 4 days after cell injection (day 0). Error bars, mean ± SEM. n = 10 per group. Two-way ANOVA: **P < .01. (F) Kaplan-Meier curve depicting percentage of tumor-free animals after rechallenge of naïve or tolinapant-cured mice with BW5147 cells. n = 10 per group.