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Fig. 3 | BMC Cancer

Fig. 3

From: Inhibition of hyperprogressive cancer disease induced by immune-checkpoint blockade upon co-treatment with meta-tyrosine and p38 pathway inhibitor

Fig. 3

Therapeutic antitumor immunological schedules against growing and residual tumors. (A, C) Antitumor vaccines. 1 × 105 MC-C (A) or LMM3 (C) cells were inoculated s.c. in the right flank. Dendritic cells (DC) were incubated with LMM3 lysate or with lysate from LMM3 cells that had been pre-treated in vitro for 24 h with different concentrations (1, 5, 10, and 20 ng/ml) of JSI-124. DC incubated with LPS served as a positive control. Negative controls were immature DC (DCi). Mice received in the left flank an antitumor vaccine (DC stimulated in vitro with MC-C lysate (A) or DC stimulated in vitro with LMM3 lysate from cells that had been treated in vitro with 20 ng/ml of JSI-124 (C), starting at day 3, 10 or 17 of tumor growth (Tumor 3D, 10D and 17D, respectively). Control mice were inoculated with immature DC (DCi). (B, D). Immune checkpoint inhibitors (ICI). 1 × 105 MC-C (B) or LMM3 (D) cells were inoculated s.c. in the right flank. Afterward, mice received anti-CTLA-4 + anti-PD-L1, starting at day 3, 10, or 17 of tumor growth. For simplicity, groups treated with anti-CTLA-4 alone and anti-PD-L1 alone were omitted. (E) Effect of vaccines and ICI on the growth of lung metastases of LMM3. Mice were treated with anti-CTLA-4 + anti-PD-L1, starting at day 3, 10, or 17 of tumor growth. Groups of mice that did not receive any treatment served as controls. (F, G) Therapeutic antitumor immunological schedules in MC-C local recurrences (F) and postsurgical LMM3 lung metastases (G). Different groups of mice received anti-CTLA-4 + anti-PD-L1, starting the day after surgery. Each dose of anti-CTLA-4 and anti-PD-L1 was 100 μg. Anti-CTLA-4 was inoculated three times a week and anti-PD-L1 for 9 consecutive days, both i.p. Cx = surgery. Data from Figures A, B, C, D, F, and G represent the mean ± SEM of two or three independent experiments. 4—6 mice per group were utilized. Statistical comparison between experimental groups and control: * p < 0.05 **; p < 0.01; ***; p < 0.001

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