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SHR Neuro Cancer Cardio Lipid Metab Microb

Wolf, S; Madanchi, M; Turko, P; Hollmén, M; Tugues, S; von, Atzigen, J; Giovanoli, P; Dummer, R; Lindenblatt, N; Halin, C; Detmar, M; Levesque, M; Gousopoulos, E.
Anti-CTLA4 treatment reduces lymphedema risk potentially through a systemic expansion of the FOXP3⁺ T_reg population.
Nat Commun. 2024; 15(1): 10784 Doi: 10.1038/s41467-024-55002-6 [OPEN ACCESS]
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Leading authors Med Uni Graz: Wolf Stefan Julian
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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 (T_reg) 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.
Find related publications in this database (using NLM MeSH Indexing): Animals - administration & dosage; T-Lymphocytes, Regulatory - immunology, drug effects; Forkhead Transcription Factors - metabolism; CTLA-4 Antigen - antagonists & inhibitors; Lymphedema - immunology, prevention & control, etiology; Mice - administration & dosage; Humans - administration & dosage; Melanoma - immunology, drug therapy; Female - administration & dosage; Male - administration & dosage; Disease Models, Animal - administration & dosage; Mice, Inbred C57BL - administration & dosage; Retrospective Studies - administration & dosage; Middle Aged - administration & dosage; Interleukin-2 Receptor alpha Subunit - metabolism