Cited by 459Immune Cell Function and InteractionCancer Immunotherapy and BiomarkersImmune cells in cancer

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A pan-cancer single-cell panorama of human natural killer cells

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Tang, Fei, Li, Jinhu, Qi, Lu, Liu, Dongfang, Bo, Yufei, Qin, Shishang, Miao, Yuhui, Yu, Kezhuo, Hou, Wenhong, Li, Jianan, Peng, Jirun, Tian, Zhigang, Zhu, Linnan, Peng, Hui, Wang, Dongfang, Zhang, Zemin·2023·Cell

DOI 10.1016/j.cell.2023.07.034

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Abstract

dendritic cells, appear to mediate the regulation of NK cell anti-tumor immunity. Our study provides insights into NK-cell-based cancer immunity and highlights potential clinical utilities of NK cell subsets as therapeutic targets.

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Metascape provides a biologist-oriented resource for the analysis of systems-level datasets
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Scenic: single-cell regulatory network inference and clustering.
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“We then identified activated regulons for both tumor-infiltrating CD56brightCD16lo and CD56dim CD16hi NK cell subsets using SCENIC.49 Importantly, the tumor-enriched c6-DNAJB1 subset exhibitedmuch higher expression of transcription factors such as KLF6 and EGR3, which are associated with the inhibition of cytotoxicity…”
Background
A guide to cancer immunotherapy: from T cell basic science to clinical practice
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RNA velocity of single cells
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The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity
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Generalizing RNA velocity to transient cell states through dynamical modeling
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Scrublet: computational identification of cell doublets in single-cell transcriptomic data
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Scrublet: computational identification of cell doublets in single-cell transcriptomic data
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Bioinformatic analysis and retrospective clinical study identifying DNAJB4 as a pan-cancer biomarker with a highlight on kidney cancer
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“Last but not least, we also evaluate the expressions of DNAJB4 in different subtypes of myeloid cell, T cell, and NK cell based on Zemin Zhang et al.’s studies (http:// panmy eloid. cancer ‐ pku. cn/,http://pan ‐ nk.cancer ‐ pku.cn/, http://cancer ‐ pku.cn: 3838/ PanCT/) [22–24].”
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Zhang, Y., He, J., Li, X., Han, Z., Chen, H., Yang, Z., & Wang, Y. (2025) · Immunologic Research · doi:10.1007/s12026-025-09665-y · Cited by 3
“It has been extensively used to study immune cell populations, track changes in gene expression during development and disease progression [30–32].”
Single-Cell Transcriptomics Reveals a Multi-Compartmental Cellular Cascade Underlying Elahere-Induced Ocular Toxicity in Rats
Zhang, J., Li, M., Yang, Y., Guo, P., Li, W., An, H., Cui, Y., Guo, L., Duan, M., Lu, Y., et al. (2025) · Pharmaceuticals · doi:10.3390/ph18101492 · Cited by 3
“In contrast, single-cell RNA sequencing (scRNA-seq) enables the dissection of individual cellular transcriptomes within heterogeneous tissues [25–27].”
Glucocorticoid Receptor Activation Reprograms NK Cells to Drive AREG‐Mediated Immunosuppression: A Pan‐Cancer Role for AREG
Qin, W. D., Liang, G., zeng, R., Li, Y., Hong, A., Wang, H., Feng, S., Wang, Y., & Wang, Y. (2025) · Advanced Science · doi:10.1002/advs.202512620 · Cited by 8
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Leng, S., Ren, Y., Tian, Y., Zhao, W., Mou, Y., Chen, X., Zhou, H., & Wang, W. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1689714 · Cited by 4
Single‐Cell RNA Sequencing of Thyroid Tissues Reveals Pathogenesis of Graves' Disease
Zhou, X., Cong, J., Peng, R., Yang, D., Dong, C., Xie, J., Yan, J., Kuang, J., Li, F., Yeap, L.-S., et al. (2025) · Advanced Science · doi:10.1002/advs.202508449 · Cited by 4
Decoding the Prognosis-Related S100A9high Monocyte in Glioblastoma Using Single-Cell and Spatial Transcriptome Sequencing
Li, X., Qin, Y., Gao, P., Wang, H., Liu, Y., Ren, L., Wu, D., & Heng, X. (2025) · OncoTargets and Therapy · doi:10.2147/ott.s553018 · Cited by 4
Inflammation-driven prognostic model and immune landscape profiling in osteosarcoma
Zhang, R., Zhou, X., & Shen, C. (2025) · Discover Oncology · doi:10.1007/s12672-025-03691-w · Cited by 3
Single-cell atlas of the tumor immune microenvironment across syngeneic murine models
Wang, J., Jiang, B., Deng, M., Yan, H., Zhang, P., Jin, W., & Shen, Z. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1676581 · Cited by 4
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Look, K., Goh, P. E., Ming, L. C., Law, S. H., Tan, S. L., Tan, E. W., Ser, H. L., & Goh, B. H. (2025) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-025-05952-x · Cited by 3
Engineering natural killer cell-derived extracellular vesicles for disease therapy
Zhang, W., Zhang, X., Zhou, Z., Xiao, L., Cheng, T., Xu, W., Xu, W., Tao, Z., Qian, H., & Shi, Y. (2025) · Journal of Controlled Release · doi:10.1016/j.jconrel.2025.114535 · Cited by 4
Comprehensive multi‐omics mapping of immune perturbations in autism spectrum disorder
Yan, C., Feng, F., Lan, C., Luo, G., Jiang, X., Wang, H., Chen, Y., Yang, Y., Deng, L., Huang, X., et al. (2025) · Clinical and Translational Medicine · doi:10.1002/ctm2.70552 · Cited by 3
Tumor immune microenvironment score predicts efficacy of immune checkpoint inhibitors-based regimens in advanced non-small cell lung cancer
Dai, J., Yan, H., Chen, Y., Zhang, Y., Ruan, Z., Ruan, Z., Tian, F., Qin, H., Xu, Q., Wang, J., et al. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-07408-z · Cited by 3
“Immune cell deconvolution analysis revealed a higher abundance of immune cell subsets, including T cells [41], NK cells [40], and DCs [23, 42], in the long-survival group compared with the short-survival group (Figure S2).”
Stress‐Programmed Immune Niches Fuel TNFR2+ Treg Activation and Drive Neoadjuvant Chemotherapy Resistance in Breast Cancer
Shao, Z., Wang, X., Zhu, H. J., Yao, L., Zhang, Q., Zhai, Z., Lv, X., Xia, X., Zhang, Y., Lu, X., et al. (2026) · Advanced Science · doi:10.1002/advs.202512952 · Cited by 3
“Another large-scale pan-cancer single-cell analysis of NK cells demonstrated that those with elevated heat shock program exhibit diminished cytotoxic potential and increased expression of immune checkpoint molecules, enriched within tumors as tumor-associated NK cells [ 18 ].”
Mechanotransduction of Piezo1 in the cancer microenvironment: implications for NK cell-based immunotherapy
Cui, X., Zhang, B., Zhao, J., & Tian, H. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2025.1729588 · Cited by 4
“Current evidence suggests that mechanosensing capacity, including the expression level and functional coupling of Piezo1, may differ across these subsets; however, systematic pro ﬁ ling of Piezo1 in human NK populations is still lacking (49).”
Immune checkpoint TIM-3 defines hyperactivated NK cells and predicts fatal outcome in severe fever with thrombocytopenia syndrome
Qian, X., Zhang, Y., Cheng, Z., Song, H., Huang, L., Jia, B., Li, J., Wang, J., & Wu, W. (2026) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0013928 · Cited by 3
“Therefore, we first isolated potential NK cells based on the positive expression of NCAM1 or KLRF1 (expression > 0) and the negative expression of CD3 genes (including CD3D , CD3G , and CD3E ) [24].”
Tislelizumab plus bevacizumab and XELOX as first-line treatment of MSS/pMMR RAS-mutant metastatic colorectal cancer (TACTIC CRC-02): a phase II study
Liu, X., Ou, K., Ma, X., Yang, W., Cao, B., Lu, J., Zhang, L., Gao, L., Wang, Q., Zhang, W., et al. (2026) · ESMO Open · doi:10.1016/j.esmoop.2025.106056 · Cited by 3
“42 Notably, these exploratory analyses of peripheral immune cells were limited by the relatively small sample size and number of available specimens, which may limit the robustness of the identified correlations.”
Targeting lncRNA-mediated networks to overcome doxorubicin resistance in cancer
Qiu, M., Wang, Z., Teng, Y., Li, M., Wu, F., & Tian, Y. (2026) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2026.105214 · Cited by 3
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Zhang, H., Shao, J., Zhao, T., Wang, Y., Shao, L., Zhu, H.-X., & Liu, J. (2026) · Human Mutation · doi:10.1155/humu/2744471 · Cited by 3
“Additionally, NK cells display potent activity against cancer stem cells (CSCs); IL-2-activated NK cells effectively target CSCs, suggesting a therapeutic strategy to prevent recurrence [39, 40].”
Norepinephrine promotes tumour cell aggressiveness and NK cell ferroptosis via ADRB2 in intrahepatic cholangiocarcinoma with perineural invasion
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“Analysis of our and two published scRNA cohorts 20 22 revealed that NK cells predominantly express β 1-and β 2-ARs (figure 5A; online supplemental figure S5A–”
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Du, X., Shi, S., & Liu, H. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1795143 · Cited by 3
“A 2023 single-cell data analysis of 716 patients published in Cell showed a signi ﬁ cant correlation between the functional state of NK cells and the risk of tumor metastasis, con ﬁ rming the clinical necessity of deeply understanding TME suppression mechanisms (60).”
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“The accumulation of these tumor-associated NK (TaNK) cells with diminished effector function predicts poor prognosis and resistance to PD-1/L1 inhibitors [22].”
CCR7+ activated dendritic cells are essential for spontaneous and immunotherapy-driven anti-tumor immunity
Koufaki, M. A., Richardson, E., Bonavita, E., Reeves, R., Moeini, A., Chiang, S., Banyard, A., Russo, M., Earnshaw, C. H., Bell, C. R., et al. (2026) · Immunity · doi:10.1016/j.immuni.2026.07.002 · Cited by 5
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Li, C. C., Liu, M., Lee, H.-P., Wu, W., & Ma, L. (2024) · Seminars in Liver Disease · doi:10.1055/s-0044-1787152 · Cited by 3
scPLAN: a hierarchical computational framework for single transcriptomics data annotation, integration and cell-type label refinement
Guo, Q., Yuan, M., Zhang, L., & Deng, M. (2024) · Briefings in Bioinformatics · doi:10.1093/bib/bbae305 · Cited by 3
“Such observation underscores the differences in NK cell composition between healthy individuals and those afflicted with tumors, corroborating prior hypotheses regarding the cytotoxicfunctionality[38,44]ofCD56-dimNKcells.”
BackgroundMethodResult
Non-Coding RNAs and Innate Immune Responses in Cancer
Díaz, C. R., Hernández‐Huerta, M. T., Mayoral, L. P.-C., Villegas, M. E. A., Zenteno, E., Cruz, M. M., Mayoral, E. P., Pina-Canseco, M. D. S., Andrade, G. M., Castellanos, A., et al. (2024) · Biomedicines · doi:10.3390/biomedicines12092072 · Cited by 3
“Using single-cell RNA sequencing (scRNA-seq) technologies, previous studies found that the regulation of Natural killer cells (NK cells) antitumor activity is mediated by a specific subpopulation of myeloid LAMP3+ dendritic cells [134].”
Method
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Maddineni, S., Sharma, K., Mohammad, I., Sherman, A. R., Štěpánek, I., Shin, J. H., Bando, J. K., & Sunwoo, J. B. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1521086 · Cited by 3
“2.12 Published single cell RNA sequencing (scRNAseq) dataset analysis scRNAseq datasets were derived from existing published data by Cella et al. and Tang et al. (31, 32).”
Influential
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Sun, L., Huai, P., Wang, Z., Zhao, Q. S., Lin, Y., Liu, T., Xue, X., Ao, S., You, J., Sun, Y., et al. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02300-0 · Cited by 3
“At recovery stage, DHS patients exhibited down-regulated expression of CCL4L2 (involved in recruitment of T cells to enhance immunity) 29,30 compared to dapsone-tolerant individuals, re ﬂ ecting a negative feedback loop to maintain homeostasis.”
Single-Cell Transcriptomics: Technical Advances, Applications and Challenges in Cancer Drug Discovery
Yang, Y., Meng, L., Zhang, T., & Tan, J. (2025) · Current Cancer Drug Targets · doi:10.2174/0115680096372729250715050452 · Cited by 3
PreDigs: A Database of Context-specific Cell Type Markers and Precise Cell Subtypes for Digestive Cell Annotation
Meng, J., Han, M., Huang, Y., Li, L., Ju, Y., Lv, D., Chen, X., Yuan, L., & Zhang, G. (2025) · Genomics Proteomics & Bioinformatics · doi:10.1093/gpbjnl/qzaf066 · Cited by 3
Elevated Proportion of Tumor-Infiltrating Natural Killer Cells Predicts Improved Survival in Peritoneal Mesothelioma: A Single-Center Study of 109 Cases
Wu, H., Wang, Y., Yang, R., Liang, X., Su, Y., Ma, R., Yang, Z., Du, X., Sun, Q., Huang, Y., et al. (2025) · Annals of Surgical Oncology · doi:10.1245/s10434-025-18335-0 · Cited by 3
“26 Dean et al. 28 discovered that NK cell functional impairment involves rapid reprogramming within the tumor microenvironment (TME), including the upregulation of inhibitory receptors (PDCD1, LAG3, HAVCR2, CD96), loss of key chemokines (CCL3, CCL4, CCL5), and diminished cytotoxic pathways.”
Lymphocyte activation gene 3 served as a potential prognostic and immunological biomarker across various cancer types: a clinical and pan‐cancer analysis
Liu, Y., Yao, Y., Yang, X., Wei, M., Lu, B., Dong, K., Lyu, D., Li, Y., Guan, W., Huang, R., et al. (2024) · Clinical & Translational Immunology · doi:10.1002/cti2.70009 · Cited by 4
Circadian rhythm related genes identified through tumorigenesis and immune infiltration-guided strategies as predictors of prognosis, immunotherapy response, and candidate drugs in skin cutaneous malignant melanoma
Liu, C., Liu, X., Cao, P., Xin, H., Li, X., & Zhu, S. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1513750 · Cited by 3
“These mechanisms are known to diminish immune system activity, potentially leading to reduced responses to immunotherapy and weakened immune surveillance, allowing tumor cells to evade recognition by the immune system (78, 79).”
Study on Heparanase Promoting Breast Cancer Cell Proliferation and Inhibiting NK Cell Cytolytic Activity Via the PD-1/PD-L1 Pathway
Qiu, J., Shen, Z., Jiang, G.-Q., & Ni, Q. (2025) · Clinical Breast Cancer · doi:10.1016/j.clbc.2025.03.012 · Cited by 3
Natural Killer Cell Dysfunction In Human Bladder Cancer Is Caused By Tissue-Specific Suppression of SLAMF6 SignalingPreprint
Farkas, A. M., Youssef, D., Tran, M. A., Balan, S., Newman, J. H., Audenet, F., Anastos, H., Velazquez, L. G., Peros, A., Ananthanarayanan, A., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.04.30.591366 · Cited by 3
“…expressed a paucity of cytolytic genes, were highly activated (CD69, HLA-DRA), immature (CD56 bright signature 67 ), imprinted with tissue residency 61,68 (CD69, CXCR6, ITGA1, ITGAE, RGS1), and had higher expression of a cytokine module that included IFNG (IFNG, TNF, CCL5, XCL1/2, FLT3LG) (Figures…”
Background
Adaptive Responses to PARP Inhibition Predict Response to Olaparib and Durvalumab: Multi-omic Analysis of Serial Biopsies in the AMTEC TrialPreprint
Mitri, Z. I., Creason, A., Stommel, J. M., Ozmen, T. Y., Rames, M. J., Ozmen, F., Bottomly, D., Jeong, B. Y., Lim, J. Y., Sivagnanam, S., et al. (2024) · medRxiv · doi:10.1101/2024.08.29.24312245 · Cited by 3
Acquisition of discrete immune suppressive barriers contributes to the initiation and progression of preinvasive to invasive human lung cancerPreprint
Yoffe, L., Bhinder, B., Kang, S. W., Zhang, H., Singh, A., Ravichandran, H., Markowitz, G. J., Martin, M., Kim, J., Zhang, C., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.12.31.630523 · Cited by 3
“NK cells have been characterized at single-cell resolution across many cancer types 58 , however, little is known about the heterogeneity and functional states of NK cells in human preinvasive nodules.”
Advances in single-cell analysis, spatial profiling, and gene editing in cancer immunogenomics
Xue, R., Cheng, J., & Zhang, N. (2025) · Holistic Integrative Oncology · doi:10.1007/s44178-024-00131-7 · Cited by 2
“Adding to this series, Zhang’ group recently performed an integrative scRNA-seq analysis on natu-ral killer (NK) cells from over 700 patients across 24 tumor types [4].”
Heterogeneity of Innate Immunity
Yu, X., & Yang, C. (2025) · Organ medicine. · doi:10.1002/orm2.70013 · Cited by 2
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Wang, X., Mei, Y., Wang, X., Wu, H., Wang, R., Zhang, P., Zhang, G., Li, J., Jiang, M., Fang, X., et al. (2025) · Clinical and Translational Medicine · doi:10.1002/ctm2.70461 · Cited by 3
“46 Initially, we obtained the cell-by-gene expression matrix at the single-tissue level.”
ScRNA-seq and Experimental Analyses Unveil Lrg1 Regulating the Oxidative Phosphorylation Pathway to Affect Neutrophil Accumulation after Cerebral Ischemia-Reperfusion
Jiang, L., Fu, L., Xiong, S., Cao, G., Mei, Y., Wu, Y., Chen, J., & Lv, Y. (2025) · Biocell · doi:10.32604/biocell.2025.068507 · Cited by 2
“For example, researchers have employed scRNA-seq to investigate [9] and have uncovered novel cellular subclusters, elucidating the complex pathophysiological mechanisms underlying cerebral tissue injury during cerebral ischemia-reperfusion. scRNA-seq facilitates a meticulous elucidation of the…”
Characteristics linking ischemia-reperfusion to chronic lung allograft dysfunction in lung transplantation: A single-cell bioinformatics analysis
Zhāng, P., Qiao, Z., Zhao, S., & Wu, K. (2025) · Transplant Immunology · doi:10.1016/j.trim.2025.102326 · Cited by 2
scPER: A Rigorous Computational Approach to Determine Cellular Subtypes in Tumors Aligned With Cancer Phenotypes From Total RNA Sequencing
Li, B., Zhou, X., & Kalluri, R. (2025) · Advanced Science · doi:10.1002/advs.202514502 · Cited by 2
Integrating Single‐Cell and Spatial Transcriptomics Reveals NK Cell Subpopulations Associated With Immunotherapy for Melanoma
Hu, Z., Chen, Y., Yang, H., Pan, Q., Li, H., Li, S., Wang, J., Huang, Y., Huang, G., & Qu, S. (2025) · Smart Medicine · doi:10.1002/smmd.70023 · Cited by 3
“NK cell subpopulations in different developmental states are simultaneously present in the tumor, suggesting that NK cell migration to the tumor may be decoupled from NK cell maturation [49].”
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Luoying, W., Xingcheng, Y., Donghang, C., Long, M., Ping, W., Zhang, L., Li, Y., Zhao, T., Hongyu, C., Wang, S., et al. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1694985 · Cited by 3
Single-cell landscape of immune cells in multiple autoimmune diseases
Zhu, L. D., Sun, W., Chen, K., Liu, Z., Tang, M., Chen, J., Shi, Y., Liu, Q., Zhang, W., Wang, J., et al. (2025) · iScience · doi:10.1016/j.isci.2025.114515 · Cited by 2
Alterations in NK Cell Function and Glucose Metabolism Characteristics in Patients With Progressive Hepatocellular Carcinoma
Yu, L., Jiang, Y., Liu, X., Yan, F., Yan, H. P., Xie, Y., Shi, W., Shang, Z., Du, J., & Yang, Z. (2026) · Immunology · doi:10.1111/imm.70095 · Cited by 2
“Natural killer (NK) cells occupy an important position in cancer immunosurveillance and can rapidly exert antitumour effects by activating receptors (e.g., NKG2D) that enhance cytotoxicity and cytokine secretion [7].”
Resident CD49a + CD103 + NKG2C + NK cells restrict HIV infection in human lymphoid tissue explants
Perea, D., Gonzalez, A., Gallego-Cortés, A., Sánchez-Gaona, N., Pumarola, F., Ortiz, N., Llano, I., Lorente, J., Falcó, V., Genescà, M., et al. (2026) · Science Advances · doi:10.1126/sciadv.adz1565 · Cited by 2
Longitudinal Plasma Metabolomics Guides Dynamic Risk Assessment and Dietary Modulation for Esophageal Squamous Cell Cancer Chemoimmunotherapy
Qian, Z.-Y., Deng, Y., Xi, M., Zhang, X. M., Sun, H., Mao, M., Luo, X.-J., Li, M., Zhang, Q., Chen, B., et al. (2026) · Cancer Discovery · doi:10.1158/2159-8290.cd-25-1449 · Cited by 2
Reinvigorating COTL1high NK cells via GITR signalling overcomes immune checkpoint blockade resistance in tsMHC-I-impaired tumours
You, W., Hu, C., Zhang, Y., Huang, Y., Yuan, J., Wu, C.-Y., Kong, D., Zhao, M., Han, Y., Li, S., et al. (2026) · Nature Cell Biology · doi:10.1038/s41556-026-01925-9 · Cited by 2
“https://doi.org/10.1038/s41556-026-01925-9 Guided by these findings and prior studies linking specific NK subsets to immunotherapy outcomes 26,27 , we performed single-cell RNA-seq (scRNA-seq) on NK cells from four treatment-naive patients with HCC with heterogeneous tsMHC-I expression.”
Influential
An AI-Enabled Single-Cell Transcriptomic Analysis Pipeline for Gene Signature Discovery in Natural Killer Cells Linked to Remission Outcomes in Chronic Myeloid Leukemia
Borra, S., Yan, D., Welner, R. S., & Yue, Z. (2026) · Biology · doi:10.3390/biology15070588 · Cited by 2
“This organization is broadly concordant with previous high-dimensional single-cell studies that have described human NK cell continua from CD56 bright cytokine producers to CD56 dim cytotoxic and tissue-or stress-adapted subsets [28,35,50,70].”
Influential
Multimodal transcriptomics reveal myCAF-derived collagen signaling associated with impaired NK-cell cytotoxicity and immune exclusion in pancreatic cancer
Kong, L., Gu, S., Wang, M., Gao, L., Song, X., & Gu, J. (2026) · Journal of Translational Medicine · doi:10.1186/s12967-026-08237-4 · Cited by 3
“Recent studies have shown that specific immune populations, such as LAMP3 + dendritic cells, could suppress NK-cell cytotoxicity within the TME [10].”
TIGIT-targeted IL-12 fusion protein engages NK and CD8+ T cells for potent tumor immunotherapy
唐卯星, Huang, Y., Bi, J., Meng, D., Zheng, X., Peng, H., Sun, R., Ma, H., Tian, Z., Sun, H., et al. (2026) · Cell Reports Medicine · doi:10.1016/j.xcrm.2026.102876 · Cited by 2
SPP1-positive macrophages drive trastuzumab resistance in HER2-positive breast cancer
Wang, D., Li, G., Lu, Y., Du, R., He, X., Sun, J., Li, D. H., Wang, S., Liu, Y., Wang, S., et al. (2026) · Cell Communication and Signaling · doi:10.1186/s12964-026-03075-9 · Cited by 2
“The gene sets of the HLA_independent inhibitor-receptor and HLA_inhibitor-receptor pathways used in the NK-cell function score are from literature reports [50], whereas the remaining pathways are from the GO and MSigDB gene sets.”
Development in the Study of Natural Killer Cells for Malignant Peritoneal Mesothelioma Treatment
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“32,33 In addition to peripheral blood, NK cells are also present in lymph nodes and a variety of nonlymphoid organs, including the liver, lung, pancreas, and uterus.”
Bioinformatics analysis reveals SOD1 is a prognostic factor in lung adenocarcinoma
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Natural Killer Cells in Cancers of Respiratory System and Their Applications in Therapeutic Approaches
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The role of TIGIT-CD226-PVR axis in mediating T cell exhaustion and apoptosis in NSCLC
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Syngeneic natural killer cell therapy activates dendritic and T cells in metastatic lungs and effectively treats low-burden metastases
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Decoding the role of lipid metabolism in NSCLC : From macrophage subtype identification to prognostic model development
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Single-cell profiling of human bone marrow reveals multiple myeloma progression is accompanied by an increase in CD56 bright bone marrow resident NK cellsPreprint
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Single-Cell Integration of Chromatin Accessibility and Transcriptomics Reveals Regulatory Networks in Ovarian Tumor-Infiltrating Adaptive NK CellsPreprint
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Single cell transcriptomic analysis reveals tumor immune infiltration by NK cells gene signature in lung adenocarcinoma
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Identification and validation of poor prognosis immunoevasive subtype of esophageal cancer with tumor-infiltrating SAMD3 + NK cell abundance
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“In addition, elevated levels of NK cells can improve the innate immune response against oncogenesis, leading to the favorable prognoses of patients with cancers (39).”
Inhibition of eEF-2K Enhances the Antitumor Efficacy of NK Cells
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Machine learning developed an immune evasion signature for predicting prognosis and immunotherapy benefits in lung adenocarcinoma
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Multi-level validation of high expression of PLAUR, FOSL2, and SLC11A1 in aortic dissection and their clinical implications
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Tumour Single‐Cell Bioinformatics: From Immune Profiling to Molecular Dynamics
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“Further subclassification revealed several functionally distinct subtypes, such as DNAJB1 + CD56 dim CD16 hi NK cell, stressed CD56 bright NK cells, effector CD56 dim NK cells and adaptive CD56 dim NK cells [26, 29].”
Influential
Unravelling key genes and molecular pathways in gastric inflammation-to-cancer transition through causal discovery: implications for early diagnosis and therapy
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Natural killer cell infiltration elicits gender‐dependent dichotomous clinical outcomes in urothelial carcinoma
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“Given that these dysfunctional NK cells commonly downregulate traditional exhaustion molecules and membrane receptors, 16,17 effective NK cell therapies may require context - specific modulation rather than broad activation strategies.”
Influential
Unleashing the potential role of tumor-associated NK cells as a novel immunotherapeutic target in triple-negative breast cancer
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“A groundbreaking study published in Cell has uncovered novel mechanisms of NK cells within the TIME, identifying a previously uncharacterized sub-type, termed TaNKs [9].”
CCDC86 modulates immune cell infiltration and disease progression in head and neck squamous cell carcinoma
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Integrated Multi-Omics Analysis Reveals Cytokine Network Dynamics and Prognostic Signatures in Hepatitis B Virus-Associated Hepatocellular Carcinoma
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ZNF683+ NK cells govern chemotherapy sensitivity in advanced HPSCC via reshaping immune microenvironment
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“…advances in single-cell transcriptome analysis provide unprecedented opportunities to comprehensively explore the immune cells in TME at a single cellular resolution, hence, single-cell RNA sequencing (scRNA-seq) has been used to analyze tumor-in ﬁ ltrating immune cells across cancers 14 – 19 .”
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“Lymphocytes, particularly CD8 + T cells and NK cells, play a crucial role in antitumor immunity, according to a tumor immunology paradigm [11, 12].”
Phenotypically similar but functionally distinct NK cell populations within the human maternal-fetal interface
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Additive anti-tumor and immunomodulatory effects of Sporoderm-removed Ganoderma lucidum spore powder and anti-PD-L1 antibody in lung cancer mice
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Functional segregation of HIF-1α and AhR controls NK cell responsiveness under hypoxia
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“Interest-ingly, these cells also showed the highest abundance of IFNG transcript in the original publication by Tang et al. 53 Similarly, the signatures repressed by HIF-1 α were enriched in mouse Hif1a-deficient NK cell infiltrating lymphomas.”
Influential
Single-cell and spatial profiling of peripheral blood and synovium unveils pro-arthritis CNBP+ myeloid cells
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Immune Checkpoint Inhibitors and Immunomodulators for Cancer Immunotherapy: Insights Into Resistance and Therapeutic Strategies
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Local cues, local killers: human natural killer cells across tissues
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Single-cell profiling uncovers a hypoxia-vascular-immune axis underlying poor immunotherapy response in acral versus cutaneous melanoma
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“Consistently, Tang et al. reported that NK cells with elevated stress responses exhibit reduced cytotoxicity and impaired anti-tumor immunity [33], suggesting the immunosuppressive NK cell component in AM.”
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Cytotoxic CD39 + tumor-associated NK cells respond to NKG2A blockade in lung cancer
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Histone lactylation-driven intratumoral IGFBP2+ NK cells promote tumor immune evasion
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Multi-Omics Analysis Reveals Nono–Kcnq2 Regulation of Neuronal Excitability in Chronic Constriction Injury-Induced Neuropathic Pain
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Single-cell transcriptomic analysis reveals the immunosuppressive status of NK cell subpopulations in TNBC
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Adipocyte-derived LTB4 programs human NKG2A + γδ T cells as cytotoxic sentinels at the adipose-tumor interface in breast cancer
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Correct stimulation of CD28H arms NK cells against tumor cells
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“The heatmap showing the expression of genes used to deﬁne immature, mature, and cytotoxic NK cells [24] highlights that NK cells from cluster 1 have a more immature proﬁle regardless of their origin.”

Authors: Tang, F., Li, J., Qi, L., Liu, D., Bo, Y., Qin, S., Miao, Y., Yu, K., Hou, W., Li, J., Peng, J., Tian, Z., Zhu, L., Peng, H., Wang, D., & Zhang, Z.
Affiliations: Peking University (CN)
Capital Medical University (CN)
Shenzhen Bay Laboratory (CN)
University of Science and Technology of China (CN)
Corresponding author: Zhu, Linnan
Peng, Hui
Wang, Dongfang
Zhang, Zemin
ORCID: Tang, Fei
Qi, Lu
Liu, Dongfang
Qin, Shishang
Miao, Yuhui
Yu, Kezhuo
Li, Jianan
Tian, Zhigang
Zhu, Linnan
Peng, Hui
Wang, Dongfang
Zhang, Zemin
Venue: Cell
Publisher: Elsevier BV
Published: 2023-09
Volume: 186
Issue: 19
Pages: 4235-4251.e20
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2023.07.034
OpenAlex: W4386034505
Cited by: 450
References: 91
Citations by year: 2026: 136 · 2025: 181 · 2024: 120 · 2023: 11
FWCI: 50.09
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Cell (publishedVersion, cc-by)
PubMed (publishedVersion)
Greater South Information System
Funders: National Natural Science Foundation of China (31991171, 592259205, 62203019, 81988101, 91959000, 92159305)
Peking University
Beijing Municipal Science and Technology Commission, Adminitrative Commission of Zhongguancun Science Park (Z221100007022002)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Keywords: natural killer cells, pan-cancer, single-cell transcriptomics, NK cell subsets, cancer immunotherapy, dendritic cells, antitumor immunity
MeSH terms: Single-Cell Gene Expression Analysis, Dendritic Cells, Humans, Immunity, Innate, Immunotherapy, Killer Cells, Natural, Neoplasms, Myeloid Cells, Tumor Microenvironment

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A pan-cancer single-cell panorama of human natural killer cells

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