The therapeutic effect of combination of ibrutinib plus CpG is T cell dependent. Mice were inoculated with H11 cells and treated with ibrutinib and intratumoral injection of CpG. Tumor outgrowth of (A) SCID mice, (B) nude mice, (C) T-cell depleted wild-type C57BL/6 mice (CD4/CD8) or both T cells were depleted by IP injection of anti-CD4 (GK1.5 clone) or anti-CD8 T cells (2.43 clone). Complete depletion of the CD8 or the CD4 T-cell populations was confirmed by flow cytometry of peripheral blood. Abs were given days 3, 2, 1, and 0 before treatment and the depletion was maintained throughout the experiment. Groups included: isotype control, CD4 T-cell–depleted, CD8 T-cell–depleted, and CD8- and CD4-cell–depleted mice. Each line represents the average left, nontreated tumor measurement of 10 mice. Two separate experiments with similar results were performed. Error bars indicate SD. NS, not significant.