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Fibrosis and secondary lymphedema: chicken or egg?

Published:April 04, 2019DOI:https://doi.org/10.1016/j.trsl.2019.04.001
      Secondary lymphedema is a common complication of cancer treatment resulting in progressive fibroadipose tissue deposition, increased risk of infections, and, in rare cases, secondary malignancies. Until recently, the pathophysiology of secondary lymphedema was thought to be related to impaired collateral lymphatic formation after surgical injury. However, more recent studies have shown that chronic inflammation-induced fibrosis plays a key role in the pathophysiology of this disease. In this review, we will discuss the evidence supporting this hypothesis and summarize recent publications demonstrating that lymphatic injury activates chronic immune responses that promote fibrosis and lymphatic leakiness, decrease collecting lymphatic pumping, and impair collateral lymphatic formation. We will review how chronic mixed T-helper cell inflammatory reactions regulate this process and how this response may be used to design novel therapies for lymphedema.

      Abbreviations:

      CCR (chemokine receptor), DCs (dendritic cells), ICAM (intercellular adhesion molecule), ICG (indocyanine green), IL (interleukin), LE (lymphedema), PCR (polymerase chain reaction), S1P (spingosine-1-phosphate), STAT (signal transducer and activator of transcription), T-bet (transcription factor expression in B-cell precursor cell line), TGF-β (transforming growth factor beta-1), Th (helper type T lymphocyte), VCAM (vascular cell adhesion molecule), VEGF (vascular endothelial growth factor), VEGFR (vascular endothelial growth factor 3)
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