Blockade of inhibitory PD-1–PD-L1 interactions and combined blockade of PD-1–PD-L1 and CTLA-4-CD80/86 interactions could further enhance effector T-cell function whereas blockade of the CD28-CD80/CD86 pathway led to significant reduction of T-cell response against ALL. Here, CD28 is linked to acute lymphoblastic leukemia.