Byemerwa Jovita, Chang Ching-Yi, McDonnell Donald P
Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USA.
Endocr Rev. 2025 Sep 16;46(5):690-708. doi: 10.1210/endrev/bnaf014.
Breast cancer remains the most commonly diagnosed malignancy among women worldwide. While breast cancer treatment outcomes have improved in recent years, there remains an unmet medical need for therapeutics that can be used with curative intent in the most aggressive breast cancer subtypes and for those cancers that have metastasized. In recent years, the success of T-cell-based therapies and other technologies that boost antitumor activities of immune cells have increased interest in using natural killer (NK) cell-based immunotherapies to treat solid tumors. These innate lymphoid cells can identify and eliminate tumor cells through their intrinsic cytotoxic activities and their ability to modulate the immune response through cytokine production. Owing to their lack of T-cell receptors, NK cells can also be used in the allogeneic setting, and strategies to develop and establish NK cells as therapeutics in breast cancer are currently being explored. In this review, we describe NK cell biology as it relates to breast cancer pathobiology and treatment outcomes and discuss how NK cell biology can be exploited and manipulated in the development of new therapeutics for breast cancer. Additionally, we review the role of estrogens in regulating NK cell activity and discuss how endocrine therapies targeting the estrogen receptor signaling axis could be employed as an approach to increase tumor immunity and the efficacy of NK-cell-directed immunotherapies.
乳腺癌仍然是全球女性中最常被诊断出的恶性肿瘤。尽管近年来乳腺癌的治疗效果有所改善，但对于可用于最具侵袭性的乳腺癌亚型以及已发生转移的癌症并具有治愈意图的疗法，仍存在未满足的医疗需求。近年来，基于T细胞的疗法以及其他增强免疫细胞抗肿瘤活性的技术取得成功，这使得人们对使用基于自然杀伤（NK）细胞的免疫疗法治疗实体瘤的兴趣增加。这些先天性淋巴细胞可以通过其内在的细胞毒性活性以及通过产生细胞因子来调节免疫反应的能力来识别和消除肿瘤细胞。由于NK细胞缺乏T细胞受体，它们也可用于同种异体环境，目前正在探索将NK细胞开发并确立为乳腺癌治疗方法的策略。在本综述中，我们描述了与乳腺癌病理生物学和治疗结果相关的NK细胞生物学，并讨论了如何在开发新的乳腺癌治疗方法中利用和操纵NK细胞生物学。此外，我们回顾了雌激素在调节NK细胞活性中的作用，并讨论了靶向雌激素受体信号轴的内分泌疗法如何可以作为一种增加肿瘤免疫力和NK细胞导向免疫疗法疗效的方法。
