Unraveling the breast cancer tumor microenvironment: crucial factors influencing natural killer cell function and therapeutic strategies

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.