Chimeric antigen receptor (CAR)?modified T cells are engineered to recognize specific tumor antigens. They have shown promising results in clinical trials, primarily in leukemia so far, but it has been difficult to predict therapeutic efficacy and toxicity for individual patients. To address this issue, Turtle et al. treated non-Hodgkin?s lymphoma patients with CAR-T cells prepared from strictly defined subsets. By carefully controlling the ratio of CD4 to CD8 T cells, the authors were able to identify some of the treatment characteristics that correlate with therapeutic response and toxicity, including the role of the drug regimen used for lymphodepletion before CAR-T cell treatment.