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 F Muzio

Research output: Contribution to journalReview articlepeer-review

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
Pages (from-to)15 - 25
Number of pages11
JournalSeminars in Cancer Biology
Volume39
DOIs
Publication statusPublished - Aug 1 2016

Keywords

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

ASJC Scopus subject areas

  • Cancer Research

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