Here we demonstrate that reconstitution of p66Shc, whose expression is profoundly impaired in CLL cells (Capitani et al., 2010), but not of the ROS-defective p66ShcQQ mutant, leads to an elevation in intracellular ROS and normalizes PD-L1 expression, restoring the ability of T cells to form ISs with leukemic cells by removing one of the most important TCR signaling blocks. This evidence concerns the gene CD274 and B-cell chronic lymphocytic leukemia.