Li Feifei, Gao Chunfang, Huang Yan, Qiao Yu, Xu Hongxiao, Liu Sheng, Wu Huangan
Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Shanghai Research Institute of Acupuncture and Meridian, Shanghai, China.
Int J Biol Sci. 2025 Mar 24;21(6):2606-2628. doi: 10.7150/ijbs.108803. eCollection 2025.
Natural killer (NK) cells have emerged as a novel and effective treatment for breast cancer. Nevertheless, the breast cancer tumor microenvironment (TME) manifests multiple immunosuppressive mechanisms, impeding the proper execution of NK cell functions. This review summarizes recent research on the influence of the TME on the functionality of NK cells in breast cancer. It delves into the effects of the internal environment of the TME on NK cells and elucidates the roles of diverse stromal components, immune cells, and signaling molecules in regulating NK cell activity within the TME. It also summarizes therapeutic strategies based on small-molecule inhibitors, antibody therapies, and natural products, as well as the progress of research in preclinical and clinical trials. By enhancing our understanding of the immunosuppressive TME and formulating strategies to counteract its effects, we could fully harness the therapeutic promise of NK cells in breast cancer treatment.
自然杀伤（NK）细胞已成为一种新型且有效的乳腺癌治疗方法。然而，乳腺癌肿瘤微环境（TME）表现出多种免疫抑制机制，阻碍了NK细胞功能的正常发挥。本综述总结了近期关于TME对乳腺癌中NK细胞功能影响的研究。它深入探讨了TME内部环境对NK细胞的影响，并阐明了各种基质成分、免疫细胞和信号分子在调节TME内NK细胞活性中的作用。它还总结了基于小分子抑制剂、抗体疗法和天然产物的治疗策略，以及临床前和临床试验的研究进展。通过加深我们对免疫抑制性TME的理解并制定应对其影响的策略，我们可以充分利用NK细胞在乳腺癌治疗中的治疗潜力。
