Ovarian cancer is the sixth leading cause of cancer-related deaths among women in the United States. This complex disease arises from tissues such as the ovarian surface epithelium, fallopian tube epithelium, endometrium, or ectopic Müllerian components and is characterized by diverse histological and molecular traits. Standard treatments like surgery, chemotherapy, and radiation have limited effectiveness and high toxicity. Targeted therapies, including poly (ADP-ribose) polymerase PARP inhibitors, anti-angiogenics, and immune checkpoint inhibitors (ICIs), face obstacles such as adaptive resistance and microenvironmental barriers that affect drug delivery and immune responses. Factors in the tumor microenvironment, such as dense stroma, hypoxia, immune suppression, cancer stem cells (CSCs), and angiogenesis, can reduce drug efficacy, worsen prognosis, and increase the risk of recurrence. Research highlights impaired immune function in ovarian cancer patients as a contributor to recurrence, emphasizing the importance of immunotherapies to target tumors and restore immune function. Preclinical studies and early clinical trials found that natural killer (NK) cell-based therapies have great potential to tackle ovarian tumors. This review explores the challenges and opportunities in treating ovarian cancer, focusing on how NK cells could help overcome these obstacles. Recent findings reveal that engineered NK cells, unlike their primary NK cells, can destroy both stem-like and differentiated ovarian tumors, pointing to their ability to target diverse tumor types. Animal studies on NK cell therapies for solid cancers have shown smaller tumor sizes, tumor differentiation in vivo, recruitment of NK and T cells in the tumor environment and peripheral tissues, restored immune function, and fewer tumor-related systemic effects—suggesting a lower chance of recurrence. NK cells clinical trials in ovarian cancer patients have also shown encouraging results, and future directions include combining NK cell therapies with standard treatments to potentially boost effectiveness.
卵巢癌是美国女性癌症相关死亡的第六大主要原因。这种复杂的疾病起源于卵巢表面上皮、输卵管上皮、子宫内膜或异位苗勒管成分等组织，其特点是具有多样化的组织学和分子特征。手术、化疗和放疗等标准治疗方法效果有限且毒性较高。靶向治疗，包括聚腺苷二磷酸核糖聚合酶（PARP）抑制剂、抗血管生成药物和免疫检查点抑制剂（ICIs），面临着适应性耐药和微环境障碍等挑战，这些障碍会影响药物递送和免疫应答。肿瘤微环境中的因素，如致密的基质、缺氧、免疫抑制、癌症干细胞（CSCs）和血管生成，可能会降低药物疗效、恶化预后并增加复发风险。研究强调卵巢癌患者免疫功能受损是导致复发的一个因素，突出了免疫疗法在靶向肿瘤和恢复免疫功能方面的重要性。临床前研究和早期临床试验发现，基于自然杀伤（NK）细胞的疗法在应对卵巢肿瘤方面具有巨大潜力。本综述探讨了治疗卵巢癌的挑战与机遇，重点关注NK细胞如何帮助克服这些障碍。最新研究显示，与原始NK细胞不同，工程化NK细胞能够同时破坏干细胞样和分化的卵巢肿瘤，这表明它们具有靶向多种肿瘤类型的能力。针对实体癌的NK细胞疗法的动物研究显示，肿瘤体积缩小、体内肿瘤分化、肿瘤环境和外周组织中NK细胞和T细胞的募集、免疫功能恢复以及肿瘤相关的全身效应减少——这表明复发可能性降低。针对卵巢癌患者的NK细胞临床试验也显示出令人鼓舞的结果，未来的方向包括将NK细胞疗法与标准治疗相结合，以潜在地提高疗效。
肿瘤(癌症)患者之家