Toll-like receptors signaling: A complex network for in B-cell lymphoid malignancies NF-kappa B activation

作者：Ntoufa Stavroula; Villa Maria Giovanna; Stamatopoulos Kostas; Ghia Paolo; Muzio Marta^*

来源：Seminars in Cancer Biology, 2016, 39: 15-25.

DOI：10.1016/j.semcancer.2016.07.001

• Toll-like receptors
• Lymphoma
• Chronic lymphocytic leukemia
• NF-kappa B
• IRAK inhibitors

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-kappa B, leading to its activation. In the present review, we summarize the literature on TLR expression and functionality and its impact on NF-kappa B 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.

• 出版日期2016-8