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Anti-CTLA4 treatment reduces lymphedema risk potentially through a systemic expansion of the FOXP3+ Treg population

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Listed:
  • Stefan Wolf

    (University Hospital Zurich, University of Zurich)

  • Matiar Madanchi

    (University Hospital Zurich, University of Zurich)

  • Patrick Turko

    (University Hospital Zurich, University of Zurich
    University Hospital Zurich, University of Zurich)

  • Maija Hollmén

    (University of Turku)

  • Sonia Tugues

    (University of Zurich)

  • Julia Atzigen

    (University Hospital Zurich, University of Zurich)

  • Pietro Giovanoli

    (University Hospital Zurich, University of Zurich)

  • Reinhard Dummer

    (University Hospital Zurich, University of Zurich)

  • Nicole Lindenblatt

    (University Hospital Zurich, University of Zurich)

  • Cornelia Halin

    (ETH Zurich)

  • Michael Detmar

    (ETH Zurich)

  • Mitchell Levesque

    (University Hospital Zurich, University of Zurich)

  • Epameinondas Gousopoulos

    (University Hospital Zurich, University of Zurich)

Abstract

Secondary lymphedema is a common sequel of oncologic surgery and presents a global health burden still lacking pharmacological treatment. The infiltration of the lymphedematous extremities with CD4+T cells influences lymphedema onset and emerges as a promising therapy target. Here, we show that the modulation of CD4+FOXP3+CD25+regulatory T (Treg) cells upon anti-CTLA4 treatment protects against lymphedema development in patients with melanoma and in a mouse lymphedema model. A retrospective evaluation of a melanoma patient registry reveals that anti-CTLA4 reduces lymphedema risk; in parallel, anti-CTLA4 reduces edema and improves lymphatic function in a mouse-tail lymphedema model. This protective effect of anti-CTLA4 correlates with a systemic expansion of Tregs, both in the animal model and in patients with melanoma. Our data thus show that anti-CTLA4 with its lymphedema-protective and anti-tumor properties is a promising candidate for more diverse application in the clinics.

Suggested Citation

  • Stefan Wolf & Matiar Madanchi & Patrick Turko & Maija Hollmén & Sonia Tugues & Julia Atzigen & Pietro Giovanoli & Reinhard Dummer & Nicole Lindenblatt & Cornelia Halin & Michael Detmar & Mitchell Leve, 2024. "Anti-CTLA4 treatment reduces lymphedema risk potentially through a systemic expansion of the FOXP3+ Treg population," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-55002-6
    DOI: 10.1038/s41467-024-55002-6
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    References listed on IDEAS

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    1. 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 & Ba, 2017. "Topical tacrolimus for the treatment of secondary lymphedema," Nature Communications, Nature, vol. 8(1), pages 1-11, April.
    2. Nicola Nosengo, 2016. "Can you teach old drugs new tricks?," Nature, Nature, vol. 534(7607), pages 314-316, June.
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