Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center New York, New York, New York 10065, USA.
Weill Cornell Medical College New York, New York, New York 10065, USA.
Nat Commun. 2017 Feb 10;8:14345. doi: 10.1038/ncomms14345.
Secondary lymphedema, a life-long complication of cancer treatment, currently has no cure. Lymphedema patients have decreased quality of life and recurrent infections with treatments limited to palliative measures. Accumulating evidence indicates that T cells play a key role in the pathology of lymphedema by promoting tissue fibrosis and inhibiting lymphangiogenesis. Here using mouse models, we show that topical therapy with tacrolimus, an anti-T-cell immunosuppressive drug, is highly effective in preventing lymphedema development and treating established lymphedema. This intervention markedly decreases swelling, T-cell infiltration and tissue fibrosis while significantly increasing formation of lymphatic collaterals with minimal systemic absorption. Animals treated with tacrolimus have markedly improved lymphatic function with increased collecting vessel contraction frequency and decreased dermal backflow. These results have profound implications for lymphedema treatment as topical tacrolimus is FDA-approved for other chronic skin conditions and has an established record of safety and tolerability.
继发性淋巴水肿是癌症治疗的一种终身并发症，目前尚无治愈方法。淋巴水肿患者的生活质量下降，且经常因治疗方法仅限于姑息措施而发生感染。越来越多的证据表明，T 细胞通过促进组织纤维化和抑制淋巴管生成在淋巴水肿的发病机制中起关键作用。在这里，我们使用小鼠模型表明，他克莫司（一种抗 T 细胞免疫抑制剂）的局部治疗对预防淋巴水肿的发展和治疗已建立的淋巴水肿非常有效。这种干预措施可显著减轻肿胀、T 细胞浸润和组织纤维化，同时显著增加淋巴管侧支形成，而全身吸收最小。用他克莫司治疗的动物具有明显改善的淋巴功能，表现为收集管收缩频率增加和真皮回流减少。这些结果对淋巴水肿治疗具有深远的意义，因为局部他克莫司已获 FDA 批准用于治疗其他慢性皮肤疾病，且具有安全性和耐受性的既定记录。
