Hossain Lazina, Gomes Karina P, Safarpour Samaneh, Gibson Spencer B
Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada; Cross Cancer Institute, Alberta Health Services, Edmonton, Alberta, Canada.
Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada; Cross Cancer Institute, Alberta Health Services, Edmonton, Alberta, Canada.
Biochim Biophys Acta Mol Basis Dis. 2025 Mar;1871(3):167677. doi: 10.1016/j.bbadis.2025.167677. Epub 2025 Jan 17.
Lymphedema is characterized by the swelling of extremities due to the accumulation of interstitial fluids. It is a painful and devastating disease that increases the risk of infections and destroys patients' quality of life. Secondary lymphedema is caused by damage to the lymphatic system due to infections, obesity, surgery, and cancer treatments. This damage fails to be repaired and leads to fluid accumulation, tissue remodeling, inflammation, and ultimately fibrosis. The lymphedema microenvironment is altered by stress, immune dysfunction, and changes in metabolism. Stress in the microenvironment includes increased hypoxia and oxidative stress but how this contributes to lymphedema progression is unclear. The immune system plays a critical role in lymphedema through T cell helper type 2 (Th2) immune responses and the infiltration of macrophages into lymphedematous tissue. The inflammatory cytokines released by immune cells lead to tissue remodeling and fibrosis. There are also changes in metabolism in the lymphedema microenvironment with altered lipid oxidation, ketone body oxidation, and glycolysis. How these changes affect lymphedema and treatment interventions has been the focus of clinical trials. Lymphedema is also associated with cancer and obesity through damage to the lymphatic system. This review will illustrate microenvironmental changes in lymphedema and how this relates to cancer and obesity. In addition, we will discuss new therapeutic strategies to treat lymphedema. Finally, we will address the prospects of lymphedema research in the context of the microenvironment.
淋巴水肿的特征是由于间质液积聚导致肢体肿胀。它是一种痛苦且具有破坏性的疾病，会增加感染风险并破坏患者的生活质量。继发性淋巴水肿是由感染、肥胖、手术和癌症治疗导致的淋巴系统损伤引起的。这种损伤无法修复，进而导致液体积聚、组织重塑、炎症，最终形成纤维化。淋巴水肿微环境会因应激、免疫功能障碍和代谢变化而改变。微环境中的应激包括缺氧和氧化应激增加，但这如何促进淋巴水肿进展尚不清楚。免疫系统通过2型辅助性T细胞（Th2）免疫反应以及巨噬细胞浸润到淋巴水肿组织中，在淋巴水肿中发挥关键作用。免疫细胞释放的炎性细胞因子会导致组织重塑和纤维化。淋巴水肿微环境中的代谢也会发生变化，脂质氧化、酮体氧化和糖酵解都会改变。这些变化如何影响淋巴水肿及治疗干预一直是临床试验的重点。淋巴水肿还通过淋巴系统损伤与癌症和肥胖相关。本综述将阐述淋巴水肿中的微环境变化以及这与癌症和肥胖的关系。此外，我们将讨论治疗淋巴水肿的新治疗策略。最后，我们将探讨在微环境背景下淋巴水肿研究的前景。
