Anti-CTLA4 treatment reduces lymphedema risk potentially through a systemic expansion of the FOXP3+ Treg population
Stefan Wolf, Matiar Madanchi, Patrick Turko, Maija Hollmén, Sònia Tugues, Julia von Atzigen, Pietro Giovanoli, Reinhard Dummer, Nicole Lindenblatt, Cornelia Halin, Michael Detmar, Mitchell P. Levesque, Epameinondas Gousopoulos
Abstract
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.