自然杀伤 (NK) 细胞是先天免疫效应细胞，其功能依赖于受体结合细胞因子、识别自身分子或检测病毒感染细胞或肿瘤细胞表达的危险信号。强大的细胞毒性潜力使 NK 细胞成为癌症免疫治疗的有希望的候选者。增强其活性的策略包括施用细胞因子、阻断免疫检查点以及设计基于抗体的 NK 细胞接合器 (NKCE)。 NKCE 代表了癌症治疗的前沿方法：它们增强 NK 与靶细胞的相互作用并优化肿瘤杀伤，可能克服免疫抑制的肿瘤微环境。 NK 细胞属于先天性淋巴样细胞 (ILC)，被分为不同的子集，还包括具有记忆样表型的细胞：这种复杂性需要在癌症免疫治疗的背景下进行探索，特别是在设计 NKCE 时。可以采用两种增强癌症患者 NK 细胞活性的策略：激活患者自身的 NK 细胞与过继转移离体激活的 NK 细胞。此外，NKCE 激活 γδ T 细胞的能力可能在免疫治疗中产生显着的协同效应。© 2024 作者。约翰·威利出版的免疫学评论

Natural killer (NK) cells are innate immune effectors whose functions rely on receptors binding cytokines, recognizing self-molecules, or detecting danger signals expressed by virus-infected or tumor cells. The potent cytotoxic potential makes NK cells promising candidates for cancer immunotherapy. To enhance their activity strategies include cytokine administration, blocking of immune checkpoints, and designing of antibody-based NK cell engagers (NKCEs). NKCEs represent a cutting-edge approach to cancer therapy: they strengthen the NK-to-target cell interactions and optimize tumor killing, possibly overcoming the immunosuppressive tumor microenvironment. NK cells belong to the innate lymphoid cells (ILCs) and are categorized into different subsets also including cells with a memory-like phenotype: this complexity needs to be explored in the context of cancer immunotherapy, particularly when designing NKCEs. Two strategies to enhance NK cell activity in cancer patients can be adopted: activating patients' own NK cells versus the adoptive transfer of ex vivo activated NK cells. Furthermore, the capability of NKCEs to activate γδ T cells could have a significant synergistic effect in immunotherapy.© 2024 The Author(s). Immunological Reviews published by John Wiley & Sons Ltd.