impairs ICOSL and MHC-I expression in DLBCL lymphomas.

Elevated 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 -driven B cell malignancy, 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 levels negatively correlate with those of both ICOSL and MHC-I in samples from DLBCL patients. We present evidence of reducing the levels of transcripts in ABC, but not in GCB primary tumors (PTs) and cell lines (CLs). In contrast, there was no evidence of targeting transcript levels in both types of DLBCLs. Nevertheless, and MHC-I levels inversely correlated in DLBCLs samples, suggesting the existence of indirect regulatory effects of . There was also evidence of dose-dependent effects at low levels. Altogether, our findings indicate that the deficiency of both ICOSL and MHC-I activity, driven by high levels of , may be causative in the failure of the host immune system to recognize and eliminate malignant B cells.