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Cited by 137Lymphatic System and DiseasesLymphatic Disorders and TreatmentsParasitic Diseases Research and Treatment

Topical tacrolimus for the treatment of secondary lymphedema

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Gardenier, Jason C., Kataru, Raghu P., Hespe, Geoffrey E., Savetsky, Ira L., Torrisi, Jeremy S., Nores, Gabriela D. García, Jowhar, Dawit K., Nitti, Matthew D. +3 more·2017·Nature Communications
DOI 10.1038/ncomms14345PMC PMC5309859
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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.

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  • CD4+ T cell inhibition with tacrolimus was effective in the mouse tail wound model, and a phase 2 clinical trial of topical tacrolimus resulted in limb volume reduction in breast cancer lymphedema patients.

    “CD4+ T cell inhibition with tacrolimus, a calcineurin inhibitor, was effective in the mouse tail wound model (149), and a phase 2 clinical trial of topical tacrolimus application resulted in limb volume reduction in breast cancer lymphedema patients (150).”

    From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [149]

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Cited by

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Authors
Gardenier, J. C., Kataru, R. P., Hespe, G. E., Savetsky, I. L., Torrisi, J. S., Nores, G. D. G., Jowhar, D. K., Nitti, M. D., Schofield, R. C., Carlow, D. C., & Mehrara, B. J.
Affiliations
  • Memorial Sloan Kettering Cancer Center (US)
  • Weill Cornell Medicine (US)
Corresponding author
Mehrara, Babak J.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2017-02-10
Volume
8
Issue
1
Pages
14345-14345
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/ncomms14345
PMC
PMC5309859
OpenAlex
W2586696305
Cited by
137
References
4
Citations by year
2026: 16 · 2025: 12 · 2024: 14 · 2023: 17 · 2022: 24 · 2021: 19 · 2020: 13 · 2019: 11 · 2018: 8 · 2017: 3
FWCI
4.22
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Memorial Sloan-Kettering Cancer Center (CA008748, 5R25CA020449)
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (R01HL111130)
  • National Cancer Institute (CA008748, T32CA009685, R21CA194882, P30CA008748, T32CA009501, R25CA020449)
Topics
  • Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
  • Health Sciences › Medicine › Surgery › Lymphatic Disorders and Treatments
  • Health Sciences › Medicine › Infectious Diseases › Parasitic Diseases Research and Treatment
Keywords
secondary lymphedema, tacrolimus, topical immunosuppressive therapy, T cells, fibrosis, lymphangiogenesis, lymphatic function, dermal backflow, cancer treatment complications
MeSH terms
Animals, Disease Models, Animal, Female, Fibrosis, Humans, Immunosuppressive Agents, Lymph Node Excision, Lymphedema, Mice, Inbred C57BL, T-Lymphocytes, Tacrolimus, Treatment Outcome, Lymphatic Vessels, Endothelial Cells

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