Toll-like receptors in the pathogenesis of human B cell malignancies

Abstract

Toll-like receptors (TLRs) are important players in B-cell activation, maturation and memory and may be involved in the pathogenesis of B-cell lymphomas. Accumulating studies show differential expression in this heterogeneous group of cancers. Stimulation with TLR specific ligands, or agonists of their ligands, leads to aberrant responses in the malignant B-cells. According to current data, TLRs can be implicated in malignant transformation, tumor progression and immune evasion processes. Most of the studies focused on multiple myeloma and chronic lymphocytic leukemia, but in the last decade the putative role of TLRs in other types of B-cell lymphomas has gained much interest. The aim of this review is to discuss recent findings on the role of TLRs in normal B cell functioning and their role in the pathogenesis of B-cell malignancies.

Quantitative Expression of Toll-Like Receptors TLR-7 and TLR-9 on Peripheral Blood Mononuclear Cells in Leukemias

“…Liang et al (2008) [24] stated that human B-ALL cell lines and primary B-ALL cells express high levels of TLR-7 mRNA and proteins. Also, Isaza-Correa et al (2014) [12] reported that in ALL cell lines, TLR-1, TLR-2, TLR-3, TLR-4, TLR-6 and TLR-7 are expressed albeit at variable levels. Although Bourke et al (2003) [15] reported that normal and malignant B cells show a distinct TLR mRNA expression profile, which includes particularly high levels of TLR-9 and TLR-10, a limited study by Reid et al (2005) suggested a lack …”

“…In ALL cell lines, TLR-1, TLR-2, TLR-3, TLR-4, TLR-6 and TLR-7 are expressed albeit at variable levels. In bone marrow of ALL patients with > 90% blasts TLR-2 mRNA can be detected in the majority of the samples [12].…”

Toll-like receptor stimulation in splenic marginal zone lymphoma can modulate cell signaling, activation and proliferation

“…26,27 Nevertheless, emerging evidence suggests that TLR may also exert a direct effect on tumor cells and may regulate tumor progression. 28,29 For example, TLR ligands induce CLL cell viability and chemoresistance in a proportion of cases. 19 Furthermore, the unabated stimulation through TLR and/or IL-1R pathways accelerates leukemia progression in a mouse model of CLL.…”

Association of Toll-Like Receptor 3 and Toll-Like Receptor 9 Single Nucleotide Polymorphisms with Hepatitis C Virus Infection and Hepatic Fibrosis in Egyptian Patients

“…3 Toll-like receptors (TLRs) are the fundamental component of the innate immune system and key regulators of acquired immunity. In humans, 10 TLRs proteins (TLR1-10) have been identified, 4 that possess different subcellular localization depending on the specific pathogen-associated molecular patterns or damage-associated molecular patterns they recognize, 5 thus called pattern recognition receptors. TLRs 1, 2, 4, 5, 6, and 10 are found on the extracellular surface of cells, whereas TLRs 3, 7, 8, and 9 are nucleic acid sensors located within the endoplasmic reticulum and endosomes.…”