Figure 5.
Late [2 weeks post-intracranial injection (wp-ic.)] blockade of CTLA-4, PD-L1 and IDO blockade decreases Treg levels and increases survival against brain tumors. (A) Timeline demonstrating the intracranial injection of 4×105 GL261 cells followed by the i.p. injection of CTLA-4 and PD-L1 mAbs at days 14, 17, 20 and 23 post-ic., the oral availability of D1-MT on days 14 through 44 post-ic. and i.p. administration of TMZ on days 14, 16, 18, as well as 21, 23 and 25 post-ic. (B) The frequency of CD4+FoxP3+ Treg and CD8+ Tc isolated from the brain, bilateral deep and superficial cervical draining lymph nodes (cLN) and the spleen of tumor-bearing mice at 3 wp-ic. (n = 5/group). (C) Survival analysis of WT mice ic. injected with 4×105 GL261 cells, alone (n = 7/group), or treated with (D)1-MT, CTLA-4 mAb (clone 9H10), PD-L1 mAb (clone 10F.9G2) and/or TMZ (n = 9 - 10/group). (D) Survival analysis of IDO−/− mice ic. injected with 4×105 GL261 cells, alone (n = 4/group), or treated with D1-MT, CTLA-4 mAb (clone 9H10), PD-L1 mAb (clone 10F.9G2) and/or TMZ (n = 7 - 8/group). *P < 0.05; **P < 0.01; ***P < 0.001.