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

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...

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Main Authors: Stefan Wolf, Matiar Madanchi, Patrick Turko, Maija Hollmén, Sonia Tugues, Julia von Atzigen, Pietro Giovanoli, Reinhard Dummer, Nicole Lindenblatt, Cornelia Halin, Michael Detmar, Mitchell Levesque, Epameinondas Gousopoulos
Format: Article
Language:English
Published: Nature Portfolio 2024-12-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-55002-6
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Summary: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.
ISSN:2041-1723