<i>miR-155</i> impairs ICOSL and MHC-I expression in DLBCL lymphomas.

Abstract

Elevated <i>miR-155</i> levels in B cell malignancies, such as CLL and DLBCL, correlate with increased aggressiveness of the disease. We recently reported that, in two different mouse models of <i>miR-155</i>-driven B cell malignancy, <i>miR-155</i> targets and down-regulates transcripts encoding ICOSL, the ligand for the Inducible T cell costimulator (ICOS), thereby impairing the capacity of T lymphocytes to recognize and eliminate malignant cells. In this report, we extend our previous findings to Human by showing that <i>miR-155</i> levels negatively correlate with those of both ICOSL and MHC-I in samples from DLBCL patients. We present evidence of <i>miR-155</i> reducing the levels of <i>ICOSL</i> transcripts in ABC, but not in GCB primary tumors (PTs) and cell lines (CLs). In contrast, there was no evidence of <i>miR-155</i> targeting <i>MHC-I</i> transcript levels in both types of DLBCLs. Nevertheless, <i>miR-155</i> and MHC-I levels inversely correlated in DLBCLs samples, suggesting the existence of indirect regulatory effects of <i>miR-155</i>. There was also evidence of dose-dependent effects at low <i>miR-155</i> levels. Altogether, our findings indicate that the deficiency of both ICOSL and MHC-I activity, driven by high levels of <i>miR-155</i>, may be causative in the failure of the host immune system to recognize and eliminate malignant B cells.