Fig. 1: Oncolytic virus upregulates IL-18 receptor expression in the TME.

a Female C57BL/6 J mice aged 4−6 weeks were implanted with B16F10 cells and treated with PBS or M1 (1.5 × 10⁷ PFU) when tumor volumes were about 200 mm³. PBS and M1 were administered via tail vein injection for 5 consecutive days. n = 10 mice per group. b−e, h Single-cell RNA-seq data for about 10,000 CD45⁺ sorted cells treated as in (a). b Distribution and frequency of different cluster in CD45⁺ cells. c Expression of select genes in each cell cluster. d Distribution and frequency of different cluster in CD8⁺ T cells. e Upregulated cytokine ligands and receptors in Teff compared to Tn. f−j Mice were treated as in (a). Mice were euthanized on the 3rd day after the last dose administration. The number of mice is the same as the individual data points in bar charts. f Changes in protein expression of chemokines after treatment with M1. g Changes in mRNA expression of cytokine receptors and ligands after treatment with M1. The fold change and q-value were calculated by DEGseq. n = 4 mice per group. h Expression of IL-18 receptor in different cluster of CD8⁺ T cells. i Proportion of naïve cells, effector and effector memory cells in CD8⁺ T cells and expression of IL-18Rα in naïve cells, effector and effector memory cells. j Changes in IL-18 receptors on CD8⁺ T cells and IL-18 ligands. k Changes in IL-18 receptors and ligands in GBM patients after treatment with oHSV-1. GBM, Glioblastoma multiforme. n = 4 patients per group. l Survival of SKCM patients with high or low expression of IL-18 receptor and ligand. SKCM, skin cutaneous melanoma. m Expression of IL-18 receptors and ligands transcripts in normal or tumor tissues from the TCGA database. In all figures, data with error bars represent mean ± SD. P-values were calculated using unpaired, two-tailed Student’s t-test (a−k) or log rank test (l).