T cells kill target cells through induction of apoptosis, either via death receptors to initiate the extrinsic apoptotic pathway, or by secreting granzymes and perforin to trigger the mitochondrial-mediated intrinsic apoptotic pathway.43 Recently, using CRISPR/Cas9 screening, two laboratories demonstrated that impaired extrinsic apoptotic signaling in tumor cells dampened CD19 CAR T cytotoxicity and drove CAR T-cell dysfunction,20,22 supporting the significance of apoptosis pathway in the CAR T-cells effectiveness. The gene discussed is PRF1; the disease is neoplasm.