St. Anna Children's Cancer Research Institute, Vienna, Austria.
Medical University of Innsbruck, Innsbruck, Austria.
Cancer Metastasis Rev. 2024 Dec;43(4):1401-1417. doi: 10.1007/s10555-024-10212-8. Epub 2024 Sep 18.
Natural killer (NK) cells have multifaceted roles within the complex tumor milieu. They are pivotal components of innate immunity and shape the dynamic landscape of tumor-immune cell interactions, and thus can be leveraged for use in therapeutic interventions. NK-based immunotherapies have had remarkable success in hematological malignancies, but these therapies are met with many challenges in solid tumors, including neuroblastoma (NB), a childhood tumor arising from the sympathetic nervous system. With a focus on NB, this review outlines the mechanisms employed by NK cells to recognize and eliminate malignant cells, delving into the dynamic relationship between ligand-receptor interactions, cytokines, and other molecules that facilitate the cross talk between NK and NB cells. We discuss the immunomodulatory functions of NK cells and the mechanisms that contribute to loss of this immunosurveillance in NB, with a focus on how this dynamic has been utilized in recent immunotherapy advancements for NB.
自然杀伤 (NK) 细胞在复杂的肿瘤微环境中具有多方面的作用。它们是先天免疫的关键组成部分，塑造了肿瘤-免疫细胞相互作用的动态景观，因此可被用于治疗干预。基于 NK 细胞的免疫疗法在血液恶性肿瘤中取得了显著成功，但这些疗法在实体瘤中面临许多挑战，包括神经母细胞瘤 (NB)，这是一种起源于交感神经系统的儿童肿瘤。本文重点关注 NB，概述了 NK 细胞识别和消除恶性细胞所采用的机制，深入探讨配体-受体相互作用、细胞因子和其他分子之间的动态关系，这些关系促进了 NK 和 NB 细胞之间的串扰。我们讨论了 NK 细胞的免疫调节功能以及导致 NB 中这种免疫监视丧失的机制，重点介绍了这种动态如何在最近用于 NB 的免疫治疗进展中得到利用。
