Natural killer cells in treatment of prostate cancer: a bibliometric analysis from basic research to clinical applications

doi:10.12307/2026.120

Abstract

Abstract: BACKGROUND: Natural killer cells have shown promising clinical applications in tumor immunotherapy in recent years, and the use of natural killer cells for the treatment of prostate cancer has attracted increasing attention. However, there is currently a lack of bibliometric analysis in this field.
OBJECTIVE: To conduct a visual analysis of the research field of natural killer cell therapy for prostate cancer using software such as CiteSpace and VOS viewer.
METHODS: The English documents are based on the Web of Science Core Collection database constructed by Clarivate Analytics and the PubMed database developed by the National Center for Biotechnology Information (NCBI), which is affiliated with the National Library of Medicine (NLM). We performed a visual analysis of the annual distribution, countries, authors, institutions, journals, and keywords of articles published over the past 10 years (2015–2025) using CiteSpace, VOS viewer, and Bibliometric websites. This analysis aimed to investigate the hotspots and trends in this research field.
RESULTS AND CONCLUSION: A total of 684 eligible studies were included in the analysis. The overall publication trend showed slight fluctuations but generally increased. According to the statistical results, the United States had the highest number of English-language publications. The author with the highest number of publications was Chen Y from the Memorial Sloan Kettering Cancer Center, with a total of 12 articles. The author with the highest number of citations was Zhang L from the Department of Physiology and Biophysics at the Zilkha Neurogenetic Institute, with a total of 629 citations. The top three institutions in terms of English-language publications were National Institutes of Health, Memorial Sloan Kettering Cancer Center, and University of California. The top three high-frequency keywords were Expression, Tumor microenvironment, and Activation. These results indicate that research on natural killer cells in the field of prostate cancer treatment has gradually increased over the past decade. Analysis of keywords and emerging terms reveals that the research hotspots in the field of natural killer cell therapy for prostate cancer are from enhancing the proliferation and cytotoxicity of natural killer cells, and the interactions between immune cells and natural killer cells to the inhibitory effects of the tumor microenvironment on natural killer cells. The research direction of natural killer cells in the treatment of prostate cancer has shifted from the initial killing and inhibitory mechanism of natural killer cells on tumor cells and enhancing the proliferation ability and cytotoxicity of natural killer cells to improving the immunotherapeutic effect of natural killer cells and the immunosuppressive effect of the tumor microenvironment on natural killer cells by regulating gene expression. How to improve the targeting and killing effects of natural killer cells is the treatment focus in this field.

Key words: natural killer cell, prostate cancer, bibliometrics, VOS viewer, CiteSpace, immunotherapy, hotspot analysis, research progress

CLC Number:

Jiang Linglong, Zhang Yuan, Shen Yuwei, Pan Jiawei, Sun Yangyang, Zhu Jundong, Fan Min, Shi Jian. Natural killer cells in treatment of prostate cancer: a bibliometric analysis from basic research to clinical applications[J]. Chinese Journal of Tissue Engineering Research, 2026, 30(13): 3474-3484.

Figures/Tables 13

References

[1] SIEGEL RL, GIAQUINTO AN, JEMAL A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74(1):12-49.
[2] SUNG H, FERLAY J, SIEGEL RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-249.
[3] JAMES ND, TANNOCK I, N’DOW J, et al. The Lancet Commission on prostate cancer: planning for the surge in cases. Lancet. 2024;403(10437):1683-1722.
[4] 张正,张莉芳,刘彦廷,等.《2022全球癌症统计报告》解读[J].中国医院统计, 2024,31(5):393-400.
[5] 鲁欣,蒋栋铭,胡明,等.2004—2018年全国前列腺癌死亡率的流行特征及时间趋势[J].上海预防医学,2021,33(10):899-904.
[6] RUAN X, ZHANG N, WANG D, et al. The Impact of Prostate-Specific Antigen Screening on Prostate Cancer Incidence and Mortality in China: 13-Year Prospective Population-Based Cohort Study. JMIR Public Health Surveill. 2024;10:e47161.
[7] HIGANO CS, SCHELLHAMMER PF, SMALL EJ, et al. Integrated data from 2 randomized, double-blind, placebo-controlled, phase 3 trials of active cellular immunotherapy with sipuleucel-T in advanced prostate cancer. Cancer. 2009; 115(16):3670-3679.
[8] 汪清,艾克拜尔·吾曼尔,王胜军,等.三种经尿道前列腺切除术治疗良性前列腺增生的疗效比较[J].现代泌尿外科杂志, 2008,13(1):44-47.
[9] CHOI E, BUIE J, CAMACHO J, et al. Evolution of Androgen Deprivation Therapy (ADT) and Its New Emerging Modalities in Prostate Cancer: An Update for Practicing Urologists, Clinicians and Medical Providers. Res Rep Urol. 2022;14:87-108.
[10] 秦庆伟,李那,王胜,等.多西他赛化疗对局限期高危前列腺癌疗效及安全性的荟萃分析[J].中华泌尿外科杂志,2019, 40(11):853-858.
[11] 沃奇军,祁小龙,刘锋,等.微创根治性前列腺切除术后非计划再次手术的原因分析及应对策略[J].中华泌尿外科杂志, 2019,40(12):905-908.
[12] 杨文博,张斌,吴佳慧,等.去势抵抗性前列腺癌免疫微环境的研究现状与治疗方向[J].中国癌症杂志,2023,33(10): 945-953.
[13] UNAL B, KUZU OF, JIN Y, et al. Targeting IRE1α reprograms the tumor microenvironment and enhances anti-tumor immunity in prostate cancer. Nat Commun. 2024;15(1):8895.
[14] LYU A, FAN Z, CLARK M, et al. Evolution of myeloid-mediated immunotherapy resistance in prostate cancer. Nature. 2025;637(8048):1207-1217.
[15] LIU S, GALAT V, GALAT Y, et al. NK cell-based cancer immunotherapy: from basic biology to clinical development. J Hematol Oncol. 2021;14(1):7.
[16] ABEL AM, YANG C, THAKAR MS, et al. Natural Killer Cells: Development, Maturation, and Clinical Utilization. Front Immunol. 2018;9:1869.
[17] PHUNG SK, ZORKO NA, SOIGNIER Y, et al. A PSMA-Targeted Tri-Specific Killer Engager Enhances NK Cell Cytotoxicity against Prostate Cancer. Cancer Immunol Res. 2025;13(2):258-272.
[18] CÓZAR B, GREPPI M, CARPENTIER S, et al. Tumor-Infiltrating Natural Killer Cells. Cancer Discov. 2021;11(1):34-44.
[19] 郑淑珍.近十年我国网络舆情研究现状及热点趋势：基于知识图谱的可视化分析[J].东南传播,2018(11):70-74.
[20] WANG F, WU L, YIN L, et al. Combined treatment with anti-PSMA CAR NK-92 cell and anti-PD-L1 monoclonal antibody enhances the antitumour efficacy against castration-resistant prostate cancer. Clin Transl Med. 2022;12(6):e901.
[21] HUSAIN Z, HUANG Y, SETH P, et al. Tumor-derived lactate modifies antitumor immune response: effect on myeloid-derived suppressor cells and NK cells. J Immunol. 2013;191(3):1486-1495.
[22] JIANG T, ZHOU C, REN S. Role of IL-2 in cancer immunotherapy. Oncoimmunology. 2016;5(6):e1163462.
[23] ROSENBERG SA, LOTZE MT, MUUL LM, et al. Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med. 1985;313(23):1485-1492.
[24] DEVILLIER R, CHRÉTIEN AS, PAGLIARDINI T, et al. Mechanisms of NK cell dysfunction in the tumor microenvironment and current clinical approaches to harness NK cell potential for immunotherapy. J Leukoc Biol. 2021;109(6):1071-1088.
[25] MANTESSO S, GEERTS D, SPANHOLTZ J, et al. Genetic Engineering of Natural Killer Cells for Enhanced Antitumor Function. Front Immunol. 2020;11:607131.
[26] DAHER M, REZVANI K. Next generation natural killer cells for cancer immunotherapy: the promise of genetic engineering. Curr Opin Immunol. 2018;51: 146-153.
[27] WU SY, FU T, JIANG YZ, et al. Natural killer cells in cancer biology and therapy. Mol Cancer. 2020;19(1):120.
[28] KWOK M, LIU R, FANG C, et al. IL-2 transpresentation promotes human NK cell expansion and cytotoxicity. J Immunol. 2011;186(11):6175-6184.
[29] 吴天根.Fidarestat通过下调AKR1B10促进NK细胞糖抗肝癌作用的研究[D].昆明:昆明医科大学,2021.
[30] JIA H, YANG H, XIONG H, et al. NK cell exhaustion in the tumor microenvironment. Front Immunol. 2023;14:1303605.
[31] ZHENG X, QIAN Y, FU B, et al. Mitochondrial fragmentation limits NK cell-based tumor immunosurveillance. Nat Immunol. 2019; 20(12):1656-1667.
[32] TERRÉN I, ORRANTIA A, VITALLÉ J, et al. NK Cell Metabolism and Tumor Microenvironment. Front Immunol. 2019; 10:2278.
[33] PORTALE F, CARRIERO R, IOVINO M, et al. C/EBPβ-dependent autophagy inhibition hinders NK cell function in cancer. Nat Commun. 2024;15(1):10343.
[34] POZNANSKI SM, SINGH K, RITCHIE TM, et al. Metabolic flexibility determines human NK cell functional fate in the tumor microenvironment. Cell Metab. 2021;33(6):1205-1220.e5.
[35] 刘敏.人外周血来源自然杀伤细胞的高效制备及其细胞毒活性表征的研究[D].北京:中国医学科学院,2021.
[36] KNORR DA, NI Z, HERMANSON D, et al. Clinical-scale derivation of natural killer cells from human pluripotent stem cells for cancer therapy. Stem Cells Transl Med. 2013;2(4):274-283.
[37] 原艺佳.基于期刊论文的国内外学术评价研究比较[D].郑州:郑州大学,2020.
[38] 王红霞,潘俊斐,蒋丹,等.嵌合抗原受体T(CAR-T)细胞体外培养体系及慢病毒侵染条件的优化[J].细胞与分子免疫学杂志,2020,36(5):390-397.
[39] 张红,吴昊,姜磊,等.人NK细胞的体外扩增及其基因表达通路的研究[J].精准医学杂志,2022,37(2):170-174.
[40] 姜红堃.原发性肾病综合征激素冲击治疗前后白细胞介素13及白细胞介素18基因表达[D].沈阳:中国医科大学,2004.
[41] FANG F, XIE S, CHEN M, et al. Advances in NK cell production. Cell Mol Immunol. 2022;19(4):460-481.
[42] YAN J, ZHANG C, XU Y, et al. GPR34 is a metabolic immune checkpoint for ILC1-mediated antitumor immunity. Nat Immunol. 2024;25(11):2057-2067.
[43] GONG Y, KLEIN WOLTERINK RGJ, WANG J, et al. Chimeric antigen receptor natural killer (CAR-NK) cell design and engineering for cancer therapy. J Hematol Oncol. 2021; 14(1):73.
[44] 卢鹏,纪猛,王皓,等.自然杀伤细胞免疫疗法在恶性肿瘤治疗中的研究进展[J].浙江理工大学学报(自然科学版), 2022,47(6):915-922.
[45] TAKAHASHI K, YAMANAKA S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006; 126(4):663-676.
[46] VAN OOST K, QUINE TA, GOVERS G, et al. The impact of agricultural soil erosion on the global carbon cycle. Science. 2007; 318(5850):626-629.
[47] LIU Y, CHAI L, LIU Y, et al. Generation of functional natural killer cells from human induced pluripotent stem cells. Cell Stem Cell. 2011;8(6):648-654.
[48] SAITO S, NISHIMURA S, ARAI Y, et al. Generation of CAR-expressing natural killer cells from human induced pluripotent stem cells. Cancer Immunol Immunother. 2016;65(11):1477-1486.