title: Topical tacrolimus for the treatment of secondary lymphedema.
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.
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center New York, New York, New York 10065, USA.
authors.forename: Jason C
authors.initials: JC
authors.lastname: Gardenier
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center New York, New York, New York 10065, USA.
authors.forename: Raghu P
authors.initials: RP
authors.lastname: Kataru
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center New York, New York, New York 10065, USA.
authors.forename: Geoffrey E
authors.identifier: 0000-0003-1961-7484
authors.initials: GE
authors.lastname: Hespe
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center New York, New York, New York 10065, USA.
authors.forename: Ira L
authors.initials: IL
authors.lastname: Savetsky
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center New York, New York, New York 10065, USA.
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Torrisi
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center New York, New York, New York 10065, USA.
authors.forename: Gabriela D García
authors.initials: GD
authors.lastname: Nores
authors.affiliation: Weill Cornell Medical College New York, New York, New York 10065, USA.
authors.forename: Dawit K
authors.initials: DK
authors.lastname: Jowhar
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center New York, New York, New York 10065, USA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Nitti
authors.affiliation: Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Schofield
authors.affiliation: Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
authors.forename: Dean C
authors.initials: DC
authors.lastname: Carlow
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center New York, New York, New York 10065, USA.
authors.forename: Babak J
authors.initials: BJ
authors.lastname: Mehrara
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D005260:Female; D005355:Fibrosis / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology; D008197:Lymph Node Excision / Q000009:adverse effects; D042601:Lymphatic Vessels / Q000187:drug effects* / Q000473:pathology; D008209:Lymphedema / Q000188:drug therapy; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000187:drug effects / Q000473:pathology; D016559:Tacrolimus / Q000008:administration & dosage / Q000494:pharmacology*; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus