乳腺癌（BC）是全球妇女癌症相关死亡的主要原因。尽管在原发肿瘤的识别和管理方面取得了重大进展，但传统疗法，包括手术，化疗和放疗无法完全消除复发和转移病情的危险。转移受到微环境和全身机制的控制，包括免疫监测。这导致了针对先天免疫系统的免疫疗法在癌症治疗中近年来受到了关注。被遗忘已久的先天免疫细胞——自然杀伤细胞（NK细胞）已经成为更有效的乳腺癌治疗的新靶点。通常情况下，NK细胞具有直接识别和清除肿瘤细胞的能力，并通过释放细胞毒性颗粒、趋化因子和促炎细胞因子来实现。然而，在乳腺癌的免疫抑制性肿瘤微环境（TME）中，NK细胞受到癌细胞的抑制信号的影响，导致其功能失调，支持肿瘤逃逸和扩散。近期已经确定了NK细胞功能失调在乳腺癌转移中的潜在机制。了解这些驱动乳腺癌转移的免疫学途径将有助于改善当前的免疫治疗策略。在本综述中，我们强调了乳腺癌如何通过使NK细胞功能失调来逃避免疫监测，并对新的NK细胞定向疗法进行了解析。版权所有 © 2023 Elsevier Inc.

Breast cancer (BC) is the main cause of cancer-related mortality among women globally. Despite substantial advances in the identification and management of primary tumors, traditional therapies including surgery, chemotherapy, and radiation cannot completely eliminate the danger of relapse and metastatic illness. Metastasis is controlled by microenvironmental and systemic mechanisms, including immunosurveillance. This led to the evolvement of immunotherapies that has gained much attention in the recent years for cancer treatment directed to the innate immune system. The long forgotten innate immune cells known as natural killer (NK) cells have emerged as novel targets for more effective therapeutics for BC. Normally, NK cells has the capacity to identify and eradicate tumor cells either directly or by releasing cytotoxic granules, chemokines and proinflammatory cytokines. Yet, NK cells are exposed to inhibitory signals by cancer cells, which causes them to become dysfunctional in the immunosuppressive tumor microenvironment (TME) in BC, supporting tumor escape and spread. Potential mechanisms of NK cell dysfunction in BC metastasis have been recently identified. Understanding these immunologic pathways driving BC metastasis will lead to improvements in the current immunotherapeutic strategies. In the current review, we highlight how BC evades immunosurveillance by rendering NK cells dysfunctional and we shed the light on novel NK cell- directed therapies.Copyright © 2023. Published by Elsevier Inc.