miRNA-Based Therapies in B Cell Non-Hodgkin Lymphoma

Non-Hodgkin lymphoma (NHL) is a diverse class of hematological cancers, many of which arise from germinal center (GC)-experienced B cells. Thus GCs, the sites of antibody affinity maturation triggered during immune responses, also provide an environment that facilitates B cell oncogenic transformation. miRNAs provide attractive and mechanistically different strategies to treat these malignancies based on their potential for simultaneous modulation of multiple targets. Here, we discuss the scientific rationale for miRNA-based therapeutics in B cell neoplasias and review recent advances that may help establish a basis for novel candidate miRNA-based therapies for B cell-NHL (B-NHL). Modulation of the expression of the oncomiRs miR-17-92, miR-21, and miR-155 and the tumor suppressor miRNAs miR-144/451, miR-181a, miR-27, miR-28-5p, and miR-34a has shown therapeutic potential in xenograft mouse models of human B-cell non-Hodgkin lymphoma (B-NHL) in vivo.Changing the expression of various miRNAs can increase sensitivity to R-CHOP chemotherapy components and B-NHL-targeted drugs such as bortezomib and imatinib in certain B-NHLs.Several miRNAs have been identified as regulators of the expression of the inhibitory receptor programmed cell death-1 (PD-1) and its ligand PD-L1. Shifting the expression of these miRNAs might contribute to the improvement of immunotherapy-based B-NHL treatments.miRNA expression patterns might be used as putative biomarkers for certain B-NHLs to predict survival, relapse, remission, and responsiveness to specific treatments.MRX34 (miR-34 mimic), mesomiR-1 (miR-16 mimic), and cobomarsen (anti-miR-155) have shown antitumor activity in Phase I clinical trials. Although not specifically designed for B-NHL, these trials included B-NHL patients.