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

A1 Refereed original research article in a scientific journal

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

Authors: Wolf, Stefan; Madanchi, Matiar; Turko, Patrick; Hollmén, Maija; Tugues, Sonia; von Atzigen, Julia; Giovanoli, Pietro; Dummer, Reinhard; Lindenblatt, Nicole; Halin, Cornelia; Detmar, Michael; Levesque, Mitchell; Gousopoulos, Epameinondas

Publisher: NATURE PORTFOLIO

Publishing place: BERLIN

Publication year: 2024

Journal: Nature Communications

Journal name in source: NATURE COMMUNICATIONS

Journal acronym: NAT COMMUN

Article number: 10784

Volume: 15

Issue: 1

Number of pages: 15

eISSN: 2041-1723

DOI: https://doi.org/10.1038/s41467-024-55002-6

Web address : https://doi.org/10.1038/s41467-024-55002-6

Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/477945662

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.

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Funding information in the publication:
Sassella Foundation, grant numbers 19/15 to EG and 21/13 to SW, Research fellowship from the Academy of Finland to MH (no. 316340), ETH Zurich (Open ETH project SKINTEGRITY.CH toMD and CH),Novartis Foundation for Medical-Biological Research (Grant 22A038) and JOBST Award (German Society of Lymphology) to EG.