Fig. 3. Adaptive immunity mediates the protective effects of tumor cell-intrinsic IRE1α loss.

a, b Top ten upregulated and ten downregulated terms enriched from GO Biological Process (Blue), Wiki Pathways (Green) and Reactome (Red) in differentially expressed genes between IRE1α^WT vs IRE1α^KO mcherry+ cells from HKP1 tumors at day 10 (a) and 14 (b). Significance cutoff values were set at log2 fold-change >0.5, p value < 0.05 and false discovery rate <10%). The count of genes enriching the GO term is represented as a barplot, and the plotted –log10 p values are represented as a dot above its corresponding bar. Genes matching these criteria were analyzed using the Enrichr portal with standard parameters. c–h Box and whisker plots of flow cytometry data from IRE1α^WT (red) vs IRE1α^KO (blue) HKP1 tumor-bearing lungs at day 10 (n = 4 IRE1α^WT and n = 6 IRE1α^KO) and 14 (n = 6 IRE1α^WT and n = 7 IRE1α^KO), showing percent viable CD45+ (c), MHCII⁺ CD11C⁺ (d), and cDC1 (e). IFNγ/TNFα⁺ T cells as a percent of CD4 (f), IFNγ/TNFα⁺ T cells as a percent of CD8 (g), and percent of T-regulatory cells of viable CD45+ cells (h). Data were shown as mean ± SD. Two-way ANOVA with Tukey’s multiple comparisons test; *P < 0.05, **P < 0.001, and ***P < 0.000, ns non-significant. i IRE1α^WT or IRE1α^KO HKP1 tumor growth in Rag2-KO mice. Data were shown as mean ± SEM of biological replicates, (n = 5, per condition). Analyses of different time points in tumor progression were performed using two-way ANOVA with Tukey’s multiple comparisons test; *P < 0.05, **P < 0.001, and ***P < 0.0001; ns non-significant. j Kaplan–Meier plots showing probability of overall survival in Rag2-KO mice bearing IRE1α^WT or IRE1α^KO HKP1 tumors. (P < 0.001, n = 5 per condition). Source data are provided as a Source Data file.