Shen Mingxin, Liu Yutong, Shao Liang, Qu Meng, Song Shixin, Sun Wei, Zhang Hao
Department of Thyroid Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.
Front Immunol. 2025 Jul 21;16:1612352. doi: 10.3389/fimmu.2025.1612352. eCollection 2025.
Natural killer cells (NK cells) are important immune cells within the tumor microenvironment (TME) and are considered the first line of defense in tumor immunity. Although many studies have focused on the role of NK cells in tumor therapy, the heterogeneity of NK cells complicates the investigation of the complex mechanisms within the tumor microenvironment. Single-cell sequencing technology, with its high-resolution capability, reveals the gene expression profiles of individual NK cells, highlighting their heterogeneity and providing more accurate information for NK cell therapy. This article begins by addressing the mechanisms underlying the formation of NK cell heterogeneity, emphasizing the significance of differentiation, development, and tissue residency in establishing this heterogeneity. It also summarizes the advances in the study of NK cell heterogeneity under physiological conditions and in tumor environments using single-cell sequencing technology. Finally, it analyzes the dynamic changes of NK cells within the tumor microenvironment under various therapeutic approaches to explore drug effects and resistance mechanisms, as well as to optimize therapeutic options. Investigating the mechanisms of tumor progression and drug intervention at the single-cell level will provide new perspectives for personalized treatment strategies centered around NK cells.
自然杀伤细胞（NK细胞）是肿瘤微环境（TME）中的重要免疫细胞，被认为是肿瘤免疫的第一道防线。尽管许多研究都聚焦于NK细胞在肿瘤治疗中的作用，但NK细胞的异质性使肿瘤微环境中复杂机制的研究变得复杂。单细胞测序技术具有高分辨率能力，可揭示单个NK细胞的基因表达谱，突出其异质性，并为NK细胞治疗提供更准确的信息。本文首先探讨NK细胞异质性形成的潜在机制，强调分化、发育和组织驻留在建立这种异质性中的重要性。还总结了利用单细胞测序技术在生理条件和肿瘤环境下NK细胞异质性研究的进展。最后，分析了在各种治疗方法下肿瘤微环境中NK细胞的动态变化，以探索药物作用和耐药机制，以及优化治疗方案。在单细胞水平上研究肿瘤进展和药物干预的机制将为以NK细胞为中心的个性化治疗策略提供新的视角。
