Transcriptomic profile of the lymphedematous tissue upon 2 weeks of anti-CTLA4 or control treatment, using the surgical mouse-tail lymphedema model

Secondary lymphedema is one of the most common side effects upon oncologic surgery and occurs in 20-40% of cancer survivors. The increased infiltration of the lymphedematous tissue with CD4+ T-cells was found to be a hallmark of lymphedema and a critical component and potential target, influencing the onset and severity of the disease. Various approaches to manipulating lymphoid cell dynamics have been successfully implemented in preclinical models, suggesting the feasibility and therapeutic potential of the applied strategy. Preliminary data of a retrospective patient cohort analysis indicated that immunomodulation with the immune-checkpoint-inhibitor anti-CTLA4 can protect against lymphedema development. The role and effect of anti-CTLA4 was subsequently evaluated in the well-established, surgically-induced murine-tail lymphedema model. Anti-CTLA4 treatment confirmed its efficacy in the applied experimental model, leading to reduced edema volumes, normalized lymphatic vascular morphology and improved lymphatic function 2 weeks post-interventionally. To better understand the mechanisms and pathway dynamics underlying the beneficial effect of anti-CTLA4, the transcriptomic profile of lymphedematous tissue of treated and control mice was assessed 2 weeks post-interventionally, using bulk sequencing of full-thickness tail skin biopsies.