Immunotransplant: Preventing unintended consequences

T-cell transfer into lymphodepleted recipients results not only in homeostatic activation of the infused cells but also in T-cell inhibition due to upregulation of immune checkpoint receptors including PD-1 and CTLA4, thereby mitigating T-cell efficacy. Dual checkpoint blockade of PD-1 and CTLA4 in conjunction with lymphodepletion—an “immunotransplant”—uncouples the T-cell inhibition from activation and amplifies the T-cell antitumor immune response.