Topical tacrolimus for the treatment of secondary lymphedema

Jason C. Gardenier, Raghu P. Kataru, Geoffrey E. Hespe, Ira L. Savetsky, Jeremy S. Torrisi, Gabriela D. García Nores, Dawit K. Jowhar, Matthew D. Nitti, Ryan C. Schofield, Dean C. Carlow and Babak J. Mehrara ()
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Jason C. Gardenier: Memorial Sloan Kettering Cancer Center New York
Raghu P. Kataru: Memorial Sloan Kettering Cancer Center New York
Geoffrey E. Hespe: Memorial Sloan Kettering Cancer Center New York
Ira L. Savetsky: Memorial Sloan Kettering Cancer Center New York
Jeremy S. Torrisi: Memorial Sloan Kettering Cancer Center New York
Gabriela D. García Nores: Memorial Sloan Kettering Cancer Center New York
Dawit K. Jowhar: Weill Cornell Medical College New York
Matthew D. Nitti: Memorial Sloan Kettering Cancer Center New York
Ryan C. Schofield: Memorial Sloan Kettering Cancer Center
Dean C. Carlow: Memorial Sloan Kettering Cancer Center
Babak J. Mehrara: Memorial Sloan Kettering Cancer Center New York

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: Abstract Secondary lymphedema, a life-long complication of cancer treatment, currently has no cure. Lymphedema patients have decreased quality of life and recurrent infections with treatments limited to palliative measures. Accumulating evidence indicates that T cells play a key role in the pathology of lymphedema by promoting tissue fibrosis and inhibiting lymphangiogenesis. Here using mouse models, we show that topical therapy with tacrolimus, an anti-T-cell immunosuppressive drug, is highly effective in preventing lymphedema development and treating established lymphedema. This intervention markedly decreases swelling, T-cell infiltration and tissue fibrosis while significantly increasing formation of lymphatic collaterals with minimal systemic absorption. Animals treated with tacrolimus have markedly improved lymphatic function with increased collecting vessel contraction frequency and decreased dermal backflow. These results have profound implications for lymphedema treatment as topical tacrolimus is FDA-approved for other chronic skin conditions and has an established record of safety and tolerability.

Date: 2017
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DOI: 10.1038/ncomms14345

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