Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou, Zhejiang, China.
Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.
Signal Transduct Target Ther. 2024 Nov 8;9(1):302. doi: 10.1038/s41392-024-02005-w.
Natural killer (NK) cells, initially identified for their rapid virus-infected and leukemia cell killing and tumor destruction, are pivotal in immunity. They exhibit multifaceted roles in cancer, viral infections, autoimmunity, pregnancy, wound healing, and more. Derived from a common lymphoid progenitor, they lack CD3, B-cell, or T-cell receptors but wield high cytotoxicity via perforin and granzymes. NK cells orchestrate immune responses, secreting inflammatory IFNγ or immunosuppressive TGFβ and IL-10. CD56 and CD56 NK cells execute cytotoxicity, while CD56 cells also regulate immunity. However, beyond the CD56 dichotomy, detailed phenotypic diversity reveals many functional subsets that may not be optimal for cancer immunotherapy. In this review, we provide comprehensive and detailed snapshots of NK cells' functions and states of activation and inhibitions in cancer, autoimmunity, angiogenesis, wound healing, pregnancy and fertility, aging, and senescence mediated by complex signaling and ligand-receptor interactions, including the impact of the environment. As the use of engineered NK cells for cancer immunotherapy accelerates, often in the footsteps of T-cell-derived engineering, we examine the interactions of NK cells with other immune effectors and relevant signaling and the limitations in the tumor microenvironment, intending to understand how to enhance their cytolytic activities specifically for cancer immunotherapy.
自然杀伤 (NK) 细胞最初因其对病毒感染和白血病细胞的快速杀伤以及肿瘤破坏作用而被识别，在免疫中起着关键作用。它们在癌症、病毒感染、自身免疫、妊娠、伤口愈合等方面具有多方面的作用。NK 细胞来源于共同的淋巴祖细胞，它们缺乏 CD3、B 细胞或 T 细胞受体，但通过穿孔素和颗粒酶发挥高细胞毒性。NK 细胞协调免疫反应，分泌炎症 IFNγ 或免疫抑制 TGFβ 和 IL-10。CD56 和 CD56 NK 细胞执行细胞毒性，而 CD56 细胞也调节免疫。然而，除了 CD56 二分法之外，详细的表型多样性揭示了许多功能亚群，这些亚群可能不适用于癌症免疫治疗。在这篇综述中，我们提供了 NK 细胞在癌症、自身免疫、血管生成、伤口愈合、妊娠和生育、衰老和衰老过程中的功能和激活状态的全面和详细的快照，这些过程由复杂的信号和配体-受体相互作用介导，包括环境的影响。随着工程化 NK 细胞在癌症免疫治疗中的应用加速，通常是在 T 细胞衍生的工程化的基础上，我们检查了 NK 细胞与其他免疫效应细胞的相互作用以及相关信号和肿瘤微环境中的限制，旨在了解如何增强它们的细胞毒性活性，专门用于癌症免疫治疗。
