CD28 and neoplasm: After establishing that the CpG + OX40-induced distant anti-tumor effect was T cell dependent (Fig. 5b) and CD19 + cells in large A20 tumors express decreased CD80 and CD86 (Fig. 3), we hypothesized the addition of anti-CTLA-4 would augment T cell activation and enhance the anti-tumor effect of CpG + OX40 in the poorly responsive, large two-tumor A20 model given that CD80/86 are involved in T cell activation through the CD28/CTLA-4 axis [31].