Antitumor T-cell Homeostatic Activation Is Uncoupled from Homeostatic Inhibition by Checkpoint Blockade.

ABSTRACT: T-cell transfer into lymphodepleted recipients induces homeostatic activation and potentiates antitumor efficacy. In contrast to canonical T-cell receptor-induced activation, homeostatic activation yields a distinct phenotype and memory state whose regulatory mechanisms are poorly understood. Here, we show in patients and murine models that, following transfer into lymphodepleted bone marrow transplant (BMT) recipients, CD8⁺ T cells undergo activation but also simultaneous homeostatic inhibition manifested by upregulation of immune-checkpoint molecules and functional suppression. T cells transferred into BMT recipients were protected from homeostatic inhibition by PD-1/CTLA4 dual checkpoint blockade (dCB). This combination of dCB and BMT-"immunotransplant"-increased T-cell homeo

SUBMITTER: Marshall N 

PROVIDER: S-EPMC6825548 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature