Anti-CTLA4 treatment reduces lymphedema risk potentially through a systemic expansion of the FOXP3+ Treg population
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<sup>+</sup>T cells influences lymphedema onset and emerges as a promising therapy target. Here, we show that the modulation of CD4<sup>+</sup>FOXP3<sup>+</sup>CD25<sup>+</sup>regulatory T (T<sub>reg</sub>) 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.
Authors
- Nicole Lindenblatt (ORCID: https://orcid.org/0000-0003-0293-1004)
- Julia von Atzigen
- Matiar Madanchi (ORCID: https://orcid.org/0000-0001-8396-3977)
- Sònia Tugues (ORCID: https://orcid.org/0000-0003-1206-3386)
- Epameinondas Gousopoulos (ORCID: https://orcid.org/0000-0002-5171-8237)
- Mitchell Paul Levesque (ORCID: https://orcid.org/0000-0001-5902-9420)
- Pietro Giovanoli (ORCID: https://orcid.org/0000-0002-2876-3312)
- Cornelia Halin (ORCID: https://orcid.org/0000-0002-7899-2850)
- Patrick Turko (ORCID: https://orcid.org/0000-0003-3695-8264)
- Michael J. Detmar (ORCID: https://orcid.org/0000-0002-5351-5054)
- Maija Hollmén (ORCID: https://orcid.org/0000-0002-3250-7653)
- Reinhard Dummer (ORCID: https://orcid.org/0000-0002-2279-6906)
- Stefan Wolf (ORCID: https://orcid.org/0000-0002-3563-3954)
Institutions
- University of Turku (FI)
- University of Zurich (CH)
- ETH Zurich (CH)
- University Hospital of Zurich (CH)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-12-30
- DOI
- https://doi.org/10.1038/s41467-024-55002-6
- Citations
- 3
- Primary Topic
- Lymphatic System and Diseases
- Type
- article
- Field-Weighted Citation Impact
- 0.85
Funders
- Novartis Foundation
- Academy of Finland
- Eidgenössische Technische Hochschule Zürich
- Novartis Stiftung für Medizinisch-Biologische Forschung
- Universität Zürich