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

Stefan Wolf, Matiar Madanchi, Patrick Turko, Maija Hollmén, Sonia Tugues, Julia Atzigen, Pietro Giovanoli, Reinhard Dummer, Nicole Lindenblatt, Cornelia Halin, Michael Detmar, Mitchell Levesque and Epameinondas Gousopoulos ()
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Stefan Wolf: University Hospital Zurich, University of Zurich
Matiar Madanchi: University Hospital Zurich, University of Zurich
Patrick Turko: 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

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-55002-6

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