miR-155 impairs ICOSL and MHC- I expression in DLBCL lymphomas

• 成果类型: Article
• 署名作者: Tili, Esmerina; Commisso, Teresa L.; Balatti, Veronica; Michaille, Jean - Jacques; Nuovo, Gerard J.; Croce, Carlo M.
• 署名单位: University System of Ohio; Ohio State University; University System of Ohio; Ohio State University; James Cancer Hospital & Solove Research Institute
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11489
• DOI: 10.1073/pnas.2422615122
• 发表日期: 2025-04-22
• 关键词: nf-kappa-b; gene-expression; cell-proliferation; microrna-155; beta-2-microglobulin; inactivation; inflammation; progression; prognosis; antigen

摘要

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 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, 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 failure of the host immune system to recognize and eliminate malignant B cells.