Leukemia cell-derived microvesicles induce T cell exhaustion via miRNA delivery.

ABSTRACT: T cell function in cancer patients is usually impaired due to the constitutive activation of immune checkpoint inhibitors. This state is known as 'exhaustion' and is often associated with the inefficient control of tumors or persistent infections. In this work, we investigated the role of leukemia cell-derived microvesicles (MVs) in T cell exhaustion. Following incubation with MVs from various sources, all T cell subtypes exhibited the exhaustion phonotype and impaired cytokine secretion in vitro. Mice models also showed the connection between immune checkpoint inhibitors and MV injection. Sequencing and bioinformatics analyses indicated that a number of transcription factors and microRNAs (miRNAs) were attributable to the dysregulation of pathways and exhaustion in T cells. Further work r

SUBMITTER: Cui J 

PROVIDER: S-EPMC5993486 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature