Ibrutinib plus intratumoral CpG induces a systemic antitumor effect in ibrutinib-sensitive tumors. C57BL/6 mice were inoculated with 1 × 106 H11 or BL3750 cells and BALB/C were inoculated with 5 × 106 A20 cells subcutaneously on both right and left of their abdomen. Tumor growth was monitored with a digital caliper. Mice were treated with ibrutinib/CpG alone or ibrutinib plus CpG. Ibrutinib (6 mg/kg) was given daily from day 8 after tumor implantation for 8 days. CpG (100 µg) was injected daily into the right tumor on days 8 to 12. (A) Schema of treatment. (B) The average tumor size of the nontreated left tumor. (C) Kaplan–Meier survival curves. On day 120, surviving mice were rechallenged with 2 × 106 H11 cells. (D-E) The average tumor size of the nontreated left tumor BL3750 and A20, respectively. Statistically significant differences (indicated by asterisks); P < .05. Each tumor model included n = 10 mice. Three separate experiments with similar results were performed. Error bars indicate SD. NS, not significant.