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




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

PublisherNATURE PORTFOLIO

BERLIN

2024

Nature Communications

NATURE COMMUNICATIONS

NAT COMMUN

10784

15

1

15

2041-1723

DOIhttps://doi.org/10.1038/s41467-024-55002-6(external)

https://doi.org/10.1038/s41467-024-55002-6(external)

https://research.utu.fi/converis/portal/detail/Publication/477945662(external)



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.


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.


Last updated on 2025-30-01 at 14:25