Fig 2: Combination of CF33-hNIS-ΔF14.5 with intra-tumoral injection of αPD-L1 results in synergistic anti-tumor effect. (a) Experimental scheme. Mice bearing single orthotopic E0771 tumors (n=7 mice for PBS group and 8 for all other groups) were treated with PBS or CF33-hNIS-ΔF14.5 (107 PFU) or α-PD-L1 Ab (100 µg) or combination of CF33-hNIS-ΔF14.5 and α-PD-L1 on each of experimental days 1, 3 and 5. All treatments were given intra-tumorally. (b) Tumor volumes in different treatment groups have been plotted. Each line represents tumor volume of an individual mouse. Numbers in parentheses indicate the number of mice that achieved complete tumor regression. (c) Per cent body weight for each treatment groups has been plotted with SEM. (d) Average tumor volume at different time points with SEM has been plotted and compared. Stats: Two-way ANOVA with Dunnett's test. (e) Mice were euthanized when tumor volume exceeded 2500 mm3 and survival of mice among the treatment groups was compared. Stats: log-rank Mantel–Cox test.

Fig 3: LTX-315-reduced ATP11B is a potential regulator of cancer immunity and PD-L1 expression. (A–B) Overall survival analysis in CD8 +T cell enriched (A) and CD8 +T cell decreased (B) patients with pancreatic cancer with low or high ATP11B expression. (C–E) Positive correlation of ATP11B with PD-L1 in pancreatic cancer. Representative images (C−D) and statistical results (E) of ATP11B and PD-L1 IHC staining in pancreatic cancer tissue microarray. (F–G) Correlation between the expression of ATP11B and abundance of immunoinhibitors (F) as well as tumor-infiltrating lymphocytes (G) across multiple human cancers, as analyzed on the The Cancer Genome Atlas database. (H–M) Maintenance of PD-L1 expression by ATP11B in multiple pancreatic cancer cell lines. Western blotting of PD-L1 expression in ATP11B KD/KO pancreatic cancer cell lines (H−I) and cell lines overexpressing ATP11B (J−K). Flow cytometry showing PD-L1 expression in ATP11B KD/KO pancreatic cancer cell lines and cell lines overexpressing ATP11B (L−M). IHC, immunohistochemical; KD, knockdown; KO, knockout; PD-L1, programmed cell death ligand 1; WT, wild type.

Fig 4: Famitinib facilitates PD-1 blockade to enhance antitumor immunity in a safe manner in vivo. A Study design and tumor growth curve in each treatment group. (n = 10 per group). B-C Tumor weight on the final day and mouse weight during treatment of each group as described above. D Proportion of CD8+ T cells among CD45+ cells and perforin+ cells among CD8+ T cells as assessed by flow cytometry. E Granzyme B and perforin expression as quantified by immunohistochemistry. F-G CD8+ and PD-L1+ cells as quantified by immunohistochemistry. Representative images of CD8 and PD-L1 staining are shown, with the mean cell number per HPF (800X) indicated. HPF, high-power field. Scale bars, 100 μm

Fig 5: Baseline biomarker results from biopsy specimens based on PFS. A Genomic events based on timing of progression following treatment (PFS event ≤ 12 versus > 12 months); asterisks indicate censoring. An exploratory forest-plot analysis of PFS according to specific somatic mutations showing unstratified hazard ratios with 95% CIs for progression. B Kaplan–Meier estimates of PFS by CD8 status and PD-L1 expression. PFS was assessed in patients with available PD-L1 staining results (n = 29). CD8 > 20% tumors were defined as CD8+. PFS, progression-free survival