We have previously shown in a humanized mouse model recapitulating EBV+ PTLD that two immunologic hallmarks associated with tumor progression are the increased expression of activation/exhaustion markers on CD8+ T cells (PD-1, LAG-3, and TIM-3) and accumulation of CD4+ Tregs (27) (28). Here, CD4 is linked to post-transplant lymphoproliferative disease.