Fig. 4: Snx9 KO improves anti-tumor efficacy and reduces terminal exhaustion in vivo.
From: Deletion of SNX9 alleviates CD8 T cell exhaustion for effective cellular cancer immunotherapy
a Schematic experimental setup of OTI Snx9 KO generation and transfer to MC38-OVA-bearing mice. b Mean and SEM of MC38-OVA tumor volumes in C57BL/6 in n = 6 mice per condition. Curves are shown until the first mouse per group reaches the humane endpoint. Statistics are pairwise 2-way ANOVAs followed by Bonferroni correction. Representative of n = 3 experiments. c Percentage of PD-1high Tim3+ OTI cells in MC38-OVA tumors in C57BL/6 mice on the indicated timepoints. n = 6 intergenic and n = 4 Snx9 KO. Statistics are 2-way ANOVA with Holm-Sidak correction. d UMAP of single-cell RNA sequencing data from OTI cells isolated from MC38-OVA tumors 13 days post-transfer. Intergenic n = 3405 cells of 5 mice and Snx9 KO n = 3612 cells of 6 mice. e Average expression of selected marker genes (color). Size = percentage of cells with detected expression for each cluster. f Proportions of each cluster in the intergenic versus the Snx9 KO sample (n = 1 from 5–6 pooled mice per condition). g Selected differentially expressed genes between intergenic and OTI Snx9 KO cells per cluster. Size indicates the -log10 adjusted p-value and color the mean log2 fold change. Statistics were derived by Seurat’s FindMarkers function. h Quantification of endogenous CD8 T cells (left) and cDC1s (right) in MC38-OVA tumors 3 days post transfer of OTI cells. Statistics are unpaired t-tests. n = 6 mice per group (i) Serum levels of IFNγ and Il-10 for days 2,8 and 15. Limit of detection (LOD) is indicated for IFNγ. Statistics are unpaired 2-way ANOVA with Holm-Sidak correction. n = 6 mice per group. j Tumor volume (mean and SEM) of NSG mice with subcutaneous MC38-OVA tumors with a transfer of OTI cells at day 12 postinjection. n = 6 mice per OTI condition, n = 4 for untreated. Statistics are pairwise 2-way ANOVAs followed by Bonferroni correction * p < 0.05, ** p < 0.01, *** p < 0.001. c, h-i Mean and SD are shown. Source data and exact p-values are provided as a Source Data file.
