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

Stavroula Ntoufa, Maria Giovanna Vilia, Kostas Stamatopoulos, Paolo Ghia, Marta Muzio

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalSeminars in Cancer Biology
DOIs
Publication statusAccepted/In press - May 6 2016

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Keywords

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

ASJC Scopus subject areas

  • Cancer Research

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