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Updated: Jul 7, 2026
Immunoglobulin Gene Sequence Analysis In Chronic Lymphocytic Leukemia: From Patient Material To Sequence Interpretation
Published on: November 26, 2018
miR-155 impairs ICOSL and MHC-I expression in DLBCL lymphomas
Esmerina Tili1,2, Teresa L Commisso2, Veronica Balatti2
1Department of Anesthesiology, Wexner Medical Center, College of Medicine, The Ohio State University, Columbus, OH 43210.
Abstract:
Elevated miR-155 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 miR-155-driven B cell malignancy, miR-155 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 miR-155 levels negatively correlate with those of both ICOSL and MHC-I in samples from DLBCL patients. We present evidence of miR-155 reducing the levels of ICOSL transcripts in ABC, but not in GCB primary tumors (PTs) and cell lines (CLs). In contrast, there was no evidence of miR-155 targeting MHC-I transcript levels in both types of DLBCLs. Nevertheless, miR-155 and MHC-I levels inversely correlated in DLBCLs samples, suggesting the existence of indirect regulatory effects of miR-155. There was also evidence of dose-dependent effects at low miR-155 levels. Altogether, our findings indicate that the deficiency of both ICOSL and MHC-I activity, driven by high levels of miR-155, may be causative in the failure of the host immune system to recognize and eliminate malignant B cells.
Insights
High microRNA-155 (miR-155) levels in B cell cancers like DLBCL reduce ICOSL and MHC-I, hindering the immune system
Area of Science:
- Immunology
- Molecular Biology
- Oncology
Background:
- Elevated microRNA-155 (miR-155) is linked to aggressive B cell malignancies, including chronic lymphocytic leukemia (CLL) and diffuse large B cell lymphoma (DLBCL).
- Previous studies in mouse models showed miR-155 down-regulates ICOSL, impairing T cell recognition of malignant cells.
Purpose of the Study:
- To investigate the role of miR-155 in human DLBCL by examining its correlation with ICOSL and MHC-I levels.
- To determine if miR-155 directly targets ICOSL and MHC-I transcripts in different DLBCL subtypes.
Main Methods:
- Analysis of miR-155, ICOSL, and MHC-I levels in human DLBCL patient samples.
- Investigation of miR-155's effect on ICOSL and MHC-I transcript levels in ABC and GCB DLBCL primary tumors and cell lines.
Main Results:
- In human DLBCL samples, miR-155 levels negatively correlated with both ICOSL and MHC-I levels.
- miR-155 reduced ICOSL transcript levels in ABC DLBCL but not GCB DLBCL.
- No direct targeting of MHC-I transcripts by miR-155 was observed, suggesting indirect regulatory mechanisms.
Conclusions:
- High miR-155 levels in DLBCL contribute to immune evasion by down-regulating ICOSL and potentially MHC-I.
- The deficiency in ICOSL and MHC-I activity, driven by elevated miR-155, may explain the host immune system's failure to eliminate malignant B cells.
