上皮性卵巢癌（EOC）仍然是最致命的妇科癌症之一。细胞因子诱导的记忆样 (CIML) 自然杀伤 (NK) 细胞在临床前和早期临床试验中显示出有希望的结果。在当前的研究中，CIML NK细胞对一组EOC细胞系表现出优异的抗肿瘤反应，增加了激活受体的表达，上调参与细胞周期/增殖的基因以及下调抑制/抑制基因。用靶向间皮素 (MSLN) 近膜结构域的嵌合抗原受体 (CAR) 转导的 CIML NK 细胞进一步改善了针对表达 MSLN 的 EOC 细胞和患者来源的异种移植肿瘤细胞的抗肿瘤反应。 CIML NK 细胞的 CAR 武装大大减少了患者来源的腹水中的功能障碍，其中与代谢改变和强直信号传导相关的转录组变化是潜在的机制。最后，MSLN-CAR CIML NK 细胞的过继转移在异种移植小鼠中表现出显着的肿瘤生长抑制作用并防止转移扩散，支持其作为 EOC 有效治疗策略的潜力。

Epithelial ovarian cancer (EOC) remains one of the most lethal gynecological cancers. Cytokine-induced memory-like (CIML) natural killer (NK) cells have shown promising results in preclinical and early-phase clinical trials. In the current study, CIML NK cells demonstrated superior antitumor responses against a panel of EOC cell lines, increased expression of activation receptors, and up-regulation of genes involved in cell cycle/proliferation and down-regulation of inhibitory/suppressive genes. CIML NK cells transduced with a chimeric antigen receptor (CAR) targeting the membrane-proximal domain of mesothelin (MSLN) further improved the antitumor responses against MSLN-expressing EOC cells and patient-derived xenograft tumor cells. CAR arming of the CIML NK cells subtanstially reduced their dysfunction in patient-derived ascites fluid with transcriptomic changes related to altered metabolism and tonic signaling as potential mechanisms. Lastly, the adoptive transfer of MSLN-CAR CIML NK cells demonstrated remarkable inhibition of tumor growth and prevented metastatic spread in xenograft mice, supporting their potential as an effective therapeutic strategy in EOC.