PDCD1 and Autoimmunity: In terms of CAR-T cells with genetic disruption of PD-1, there could be an increased risk of autoimmunity due to breakdown of peripheral immune tolerance for the following reasons: (1) the threshold for T cell receptor (TCR)-mediated self-reactive T cell activation might be lower due to stimulation received by engagement of the specific CAR antigen and (2) self-reactive T cells could be expanded to a greater level as a consequence of CAR-mediated expansion, worsening autoimmune activity.