Unraveling NK cell heterogeneity through single-cell sequencing: insights from physiological and tumor contexts for clinical applications

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...

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Main Authors: Mingxin Shen, Yutong Liu, Liang Shao, Meng Qu, Shixin Song, Wei Sun, Hao Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1612352/full
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author Mingxin Shen
Yutong Liu
Liang Shao
Meng Qu
Shixin Song
Wei Sun
Hao Zhang
author_facet Mingxin Shen
Yutong Liu
Liang Shao
Meng Qu
Shixin Song
Wei Sun
Hao Zhang
author_sort Mingxin Shen
collection DOAJ
description 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.
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institution Kabale University
issn 1664-3224
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publishDate 2025-07-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Immunology
spelling doaj-art-f75dfdcdb31c45ce876cd16f94288e132025-08-20T03:28:19ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.16123521612352Unraveling NK cell heterogeneity through single-cell sequencing: insights from physiological and tumor contexts for clinical applicationsMingxin Shen0Yutong Liu1Liang Shao2Meng Qu3Shixin Song4Wei Sun5Hao Zhang6Department of Thyroid Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, ChinaDepartment of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Thyroid Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, ChinaDepartment of Thyroid Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, ChinaDepartment of Thyroid Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, ChinaDepartment of Thyroid Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, ChinaDepartment of Thyroid Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, ChinaNatural 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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1612352/fullsingle-RNA sequencingNK cellheterogeneitytumor microenvironmentdrug intervention
spellingShingle Mingxin Shen
Yutong Liu
Liang Shao
Meng Qu
Shixin Song
Wei Sun
Hao Zhang
Unraveling NK cell heterogeneity through single-cell sequencing: insights from physiological and tumor contexts for clinical applications
Frontiers in Immunology
single-RNA sequencing
NK cell
heterogeneity
tumor microenvironment
drug intervention
title Unraveling NK cell heterogeneity through single-cell sequencing: insights from physiological and tumor contexts for clinical applications
title_full Unraveling NK cell heterogeneity through single-cell sequencing: insights from physiological and tumor contexts for clinical applications
title_fullStr Unraveling NK cell heterogeneity through single-cell sequencing: insights from physiological and tumor contexts for clinical applications
title_full_unstemmed Unraveling NK cell heterogeneity through single-cell sequencing: insights from physiological and tumor contexts for clinical applications
title_short Unraveling NK cell heterogeneity through single-cell sequencing: insights from physiological and tumor contexts for clinical applications
title_sort unraveling nk cell heterogeneity through single cell sequencing insights from physiological and tumor contexts for clinical applications
topic single-RNA sequencing
NK cell
heterogeneity
tumor microenvironment
drug intervention
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1612352/full
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