Jiang Weiyu, Xu Wen, Chen Feng
Department of Obstetrics, Obstetrics and Gynecology Center, The First Hospital of Jilin University, Changchun, Jilin, China.
Department of General Gynecology I, Obstetrics and Gynecology Center, The First Hospital of Jilin University, Changchun, Jilin, China.
Front Immunol. 2025 Sep 5;16:1657605. doi: 10.3389/fimmu.2025.1657605. eCollection 2025.
Endometriosis (EMs) is a chronic inflammatory disorder characterized by dysregulated innate immunity, particularly impaired cytotoxic function of natural killer (NK) cells. As pivotal effectors of the innate immune response, NK cells fail to eliminate ectopic endometrial lesions due to aberrant receptor-ligand interactions, elevated levels of immunosuppressive cytokines (TGF-β, IL-6, and IL-10), and dysfunction of adhesion molecules. This compromised immune surveillance facilitates the survival and implantation of ectopic lesions, contributing to the hallmark symptoms of pain and infertility. Recent immunotherapeutic strategies, including NK cell checkpoint blockade (anti-NKG2A, anti-PD-1), IL-2-based activation, and adoptive NK cell transfer-seek to restore NK cell cytotoxicity and reestablish immune homeostasis. This review summarizes current advances in understanding NK cell dysfunction in EMs, emphasizing its central role in immune evasion and the therapeutic promise of targeting innate immune pathways.
子宫内膜异位症（EMs）是一种慢性炎症性疾病，其特征是固有免疫失调，特别是自然杀伤（NK）细胞的细胞毒性功能受损。作为固有免疫反应的关键效应细胞，由于异常的受体-配体相互作用、免疫抑制细胞因子（转化生长因子-β、白细胞介素-6和白细胞介素-10）水平升高以及黏附分子功能障碍，NK细胞无法清除异位子宫内膜病变。这种受损的免疫监视促进了异位病变的存活和植入，导致了疼痛和不孕等标志性症状。最近的免疫治疗策略，包括NK细胞检查点阻断（抗NKG2A、抗PD-1）、基于白细胞介素-2的激活以及过继性NK细胞转移，旨在恢复NK细胞的细胞毒性并重建免疫稳态。本综述总结了目前在理解EMs中NK细胞功能障碍方面的进展，强调了其在免疫逃逸中的核心作用以及靶向固有免疫途径的治疗前景。
