MiR-149-3p reverses CD8⁺ T-cell exhaustion by reducing inhibitory receptors and promoting cytokine secretion in breast cancer cells.

ABSTRACT: Blockade of inhibitory receptors (IRs) is one of the most effective immunotherapeutic approaches to treat cancer. Dysfunction of miRNAs is a major cause of aberrant expression of IRs and contributes to the immune escape of cancer cells. How miRNAs regulate immune checkpoint proteins in breast cancer remains largely unknown. In this study, downregulation of miRNAs was observed in PD-1-overexpressing CD8⁺ T cells using miRNA array analysis of mouse breast cancer homografts. The data reveal that miR-149-3p was predicted to bind the 3'UTRs of mRNAs encoding T-cell inhibitor receptors PD-1, TIM-3, BTLA and Foxp1. Treatment of CD8⁺ T cells with an miR-149-3p mimic reduced apoptosis, attenuated changes in mRNA markers of T-cell exhaustion and downregulated mRNAs encoding PD-

SUBMITTER: Zhang M 

PROVIDER: S-EPMC6833224 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature