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

Semin Cancer Biol. 2016 Aug;39:15-25. doi: 10.1016/j.semcancer.2016.07.001. Epub 2016 Jul 9.


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.

Keywords: Chronic lymphocytic leukemia; IRAK inhibitors; Lymphoma; NF-κB; Toll-like receptors.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / metabolism
  • Lymphoma, B-Cell / metabolism*
  • Lymphoma, B-Cell / pathology
  • Myeloid Differentiation Factor 88 / metabolism
  • NF-kappa B / metabolism*
  • Polymorphism, Genetic
  • Signal Transduction
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / metabolism*


  • MYD88 protein, human
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • Toll-Like Receptors