title: Toll-like receptors signaling: A complex network for NF-κB activation in B-cell lymphoid malignancies.
abstract: Malignancies of mature B cells are quite distinctive in originating from well-differentiated cells. Hence, it is not paradoxical that, similar to their normal counterparts, most mature B cell lymphoma subtypes are critically dependent on microenvironmental cues. Such external signals are sensed by various receptors present on the malignant cells, including the Toll-like receptors (TLRs), eliciting a range of cellular responses, including proliferation but also anergy and apoptosis, often with disease-specific patterns. Critically, the TLR signaling pathways are intertwined with other receptor pathways in malignant B cells, most notably the B-cell receptor pathway, and converge on NF-κB, leading to its activation. In the present review, we summarize the literature on TLR expression and functionality and its impact on NF-κB activation in different B cell malignancies including chronic lymphocytic leukemia where TLR9 induces activation, cell proliferation and chemoresistance in a proportion of patients while apoptosis can be induced in others. Additionally, we also discuss the therapeutic potential of strategies targeting TLR signaling in lymphoma.
authors.affiliation: Institute of Applied Biosciences, CERTH, Thessaloniki, Greece; Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Stavroula
authors.initials: S
authors.lastname: Ntoufa
authors.affiliation: Division of Experimental Oncology, IRCCS San Raffaele Hospital, Milano, Italy.
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Vilia
authors.affiliation: Institute of Applied Biosciences, CERTH, Thessaloniki, Greece; Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Kostas
authors.initials: K
authors.lastname: Stamatopoulos
authors.affiliation: Division of Experimental Oncology, IRCCS San Raffaele Hospital, Milano, Italy; Università Vita-Salute San Raffaele, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Ghia
authors.affiliation: Division of Experimental Oncology, IRCCS San Raffaele Hospital, Milano, Italy. Electronic address: muzio.marta@hsr.it.
authors.forename: Marta
authors.initials: M
authors.lastname: Muzio
mesh_terms: D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000378:metabolism* / Q000473:pathology; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D011110:Polymorphism, Genetic; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism*
chemical_list: C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D051193:Toll-Like Receptors
keywords: Chronic lymphocytic leukemia; IRAK inhibitors; Lymphoma; NF-κB; Toll-like receptors