肿瘤相关中性粒细胞的分型及其鉴定方法研究进展
Research Progress on Typing and Identification Methods of Tumor Associated Neutrophils
DOI: 10.12677/wjcr.2026.161001, PDF,    科研立项经费支持
作者: 常伦惠, 张国龙*：安徽理工大学第一附属医院，安徽 淮南；同济大学附属皮肤病医院光医学治疗科，上海；严国荣：同济大学附属皮肤病医院光医学治疗科，上海
关键词: 肿瘤相关中性粒细胞；肿瘤微环境；异质性；分子特征；鉴定；Tumor-associated neutrophils (TANs)； Tumor microenvironment (TME)； Heterogeneity； Molecular characteristics； Identification
摘要: 中性粒细胞是人类血液中最丰富的免疫细胞，存在于肿瘤微环境中的中性粒细胞称为肿瘤相关中性粒细胞(Tumor-associated neutrophils, TANs)，在肿瘤发生发展中发挥重要作用。近年来，多项研究表明，TANs与传统中性粒细胞相比显著不同，并存在N1和N2等多种异质性亚型，发挥抗瘤和促瘤双重效应。然而，目前尚无统一的方法对TANs进行精准鉴定。本文综述了TANs的分子特征及鉴定方法，有望为TANs的相关研究提供借鉴意义。
Abstract: Neutrophils are the most abundant immune cells in human blood. Neutrophils that infiltrate the tumor microenvironment are termed tumor-associated neutrophils (TANs), which play pivotal roles in tumor initiation and progression. In recent years, accumulating studies have demonstrated that TANs exhibit distinct biological characteristics compared with their conventional counterparts in circulation, and they consist of heterogeneous subsets such as N1 and N2 phenotypes, exerting dual pro-tumorigenic and anti-tumorigenic effects. However, a standardized protocol for the accurate identification of TANs has not been established to date. This review summarizes the molecular features and identification methods of TANs, aiming to provide valuable insights for future research in this field.
文章引用：常伦惠, 严国荣, 张国龙. 肿瘤相关中性粒细胞的分型及其鉴定方法研究进展[J]. 世界肿瘤研究, 2026, 16(1): 1-7. https://doi.org/10.12677/wjcr.2026.161001

参考文献

[1] Mayadas, T.N., Cullere, X. and Lowell, C.A. (2014) The Multifaceted Functions of Neutrophils. Annual Review of Pathology: Mechanisms of Disease, 9, 181-218. [Google Scholar] [CrossRef] [PubMed]
[2] Jensen, H.K., Donskov, F., Marcussen, N., Nordsmark, M., Lundbeck, F. and von der Maase, H. (2009) Presence of Intratumoral Neutrophils Is an Independent Prognostic Factor in Localized Renal Cell Carcinoma. Journal of Clinical Oncology, 27, 4709-4717. [Google Scholar] [CrossRef] [PubMed]
[3] SenGupta, S., Subramanian, B.C. and Parent, C.A. (2018) Getting Tanned: How the Tumor Microenvironment Drives Neutrophil Recruitment. Journal of Leukocyte Biology, 105, 449-462. [Google Scholar] [CrossRef] [PubMed]
[4] Adrover, J.M., Nicolás-Ávila, J.A. and Hidalgo, A. (2016) Aging: A Temporal Dimension for Neutrophils. Trends in Immunology, 37, 334-345. [Google Scholar] [CrossRef] [PubMed]
[5] Basu, S., Hodgson, G., Katz, M. and Dunn, A.R. (2002) Evaluation of Role of G-CSF in the Production, Survival, and Release of Neutrophils from Bone Marrow into Circulation. Blood, 100, 854-861. [Google Scholar] [CrossRef] [PubMed]
[6] Galli, S.J., Borregaard, N. and Wynn, T.A. (2011) Phenotypic and Functional Plasticity of Cells of Innate Immunity: Macrophages, Mast Cells and Neutrophils. Nature Immunology, 12, 1035-1044. [Google Scholar] [CrossRef] [PubMed]
[7] Mayadas, T.N. and Cullere, X. (2005) Neutrophil Β2 Integrins: Moderators of Life or Death Decisions. Trends in Immunology, 26, 388-395. [Google Scholar] [CrossRef] [PubMed]
[8] Dancey, J.T., Deubelbeiss, K.A., Harker, L.A. and Finch, C.A. (1976) Neutrophil Kinetics in Man. Journal of Clinical Investigation, 58, 705-715. [Google Scholar] [CrossRef] [PubMed]
[9] Pillay, J., den Braber, I., Vrisekoop, N., Kwast, L.M., de Boer, R.J., Borghans, J.A.M., et al. (2010) In Vivo Labeling with 2H2O Reveals a Human Neutrophil Lifespan of 5.4 Days. Blood, 116, 625-627. [Google Scholar] [CrossRef] [PubMed]
[10] Tofts, P.S., Chevassut, T., Cutajar, M., Dowell, N.G. and Peters, A.M. (2011) Doubts Concerning the Recently Reported Human Neutrophil Lifespan of 5.4 Days. Blood, 117, 6050-6052. [Google Scholar] [CrossRef] [PubMed]
[11] Ng, M.S.F., Kwok, I., Tan, L., Shi, C., Cerezo-Wallis, D., Tan, Y., et al. (2024) Deterministic Reprogramming of Neutrophils within Tumors. Science, 383, eadf6493. [Google Scholar] [CrossRef] [PubMed]
[12] Cassetta, L. and Pollard, J.W. (2018) Targeting Macrophages: Therapeutic Approaches in Cancer. Nature Reviews Drug Discovery, 17, 887-904. [Google Scholar] [CrossRef] [PubMed]
[13] Fridlender, Z.G., Sun, J., Kim, S., Kapoor, V., Cheng, G., Ling, L., et al. (2009) Polarization of Tumor-Associated Neutrophil Phenotype by TGF-β: “N1” versus “N2” TAN. Cancer Cell, 16, 183-194. [Google Scholar] [CrossRef] [PubMed]
[14] Shaul, M.E. and Fridlender, Z.G. (2019) Tumour-Associated Neutrophils in Patients with Cancer. Nature Reviews Clinical Oncology, 16, 601-620. [Google Scholar] [CrossRef] [PubMed]
[15] Ohms, M., Möller, S. and Laskay, T. (2020) An Attempt to Polarize Human Neutrophils toward N1 and N2 Phenotypes in Vitro. Frontiers in Immunology, 11, Article ID: 532. [Google Scholar] [CrossRef] [PubMed]
[16] Mantovani, A., Cassatella, M.A., Costantini, C. and Jaillon, S. (2011) Neutrophils in the Activation and Regulation of Innate and Adaptive Immunity. Nature Reviews Immunology, 11, 519-531. [Google Scholar] [CrossRef] [PubMed]
[17] Granot, Z., Henke, E., Comen, E.A., King, T.A., Norton, L. and Benezra, R. (2011) Tumor Entrained Neutrophils Inhibit Seeding in the Premetastatic Lung. Cancer Cell, 20, 300-314. [Google Scholar] [CrossRef] [PubMed]
[18] Masucci, M.T., Minopoli, M. and Carriero, M.V. (2019) Tumor Associated Neutrophils. Their Role in Tumorigenesis, Metastasis, Prognosis and Therapy. Frontiers in Oncology, 9, Article ID: 1146. [Google Scholar] [CrossRef] [PubMed]
[19] Wang, L., Liu, Y., Dai, Y., Tang, X., Yin, T., Wang, C., et al. (2023) Single-Cell RNA-Seq Analysis Reveals Bhlhe40-Driven Pro-Tumour Neutrophils with Hyperactivated Glycolysis in Pancreatic Tumour Microenvironment. Gut, 72, 958-971. [Google Scholar] [CrossRef] [PubMed]
[20] Wu, Y., Ma, J., Yang, X., Nan, F., Zhang, T., Ji, S., et al. (2024) Neutrophil Profiling Illuminates Anti-Tumor Antigen-Presenting Potency. Cell, 187, 1422-1439.e24. [Google Scholar] [CrossRef] [PubMed]
[21] Mishalian, I., Bayuh, R., Levy, L., Zolotarov, L., Michaeli, J. and Fridlender, Z.G. (2013) Tumor-Associated Neutrophils (TAN) Develop Pro-Tumorigenic Properties during Tumor Progression. Cancer Immunology, Immunotherapy, 62, 1745-1756. [Google Scholar] [CrossRef] [PubMed]
[22] Andzinski, L., Kasnitz, N., Stahnke, S., Wu, C., Gereke, M., von Köckritz‐Blickwede, M., et al. (2016) Type IIFNs Induce Anti‐Tumor Polarization of Tumor Associated Neutrophils in Mice and Human. International Journal of Cancer, 138, 1982-1993. [Google Scholar] [CrossRef] [PubMed]
[23] Borregaard, N. (2010) Neutrophils, from Marrow to Microbes. Immunity, 33, 657-670. [Google Scholar] [CrossRef] [PubMed]
[24] Zhu, Y.P., Padgett, L., Dinh, H.Q., Marcovecchio, P., Blatchley, A., Wu, R., et al. (2018) Identification of an Early Unipotent Neutrophil Progenitor with Pro-Tumoral Activity in Mouse and Human Bone Marrow. Cell Reports, 24, 2329-2341.e8. [Google Scholar] [CrossRef] [PubMed]
[25] Sagiv, J.Y., Michaeli, J., Assi, S., Mishalian, I., Kisos, H., Levy, L., et al. (2015) Phenotypic Diversity and Plasticity in Circulating Neutrophil Subpopulations in Cancer. Cell Reports, 10, 562-573. [Google Scholar] [CrossRef] [PubMed]
[26] Brandau, S., Trellakis, S., Bruderek, K., Schmaltz, D., Steller, G., Elian, M., et al. (2011) Myeloid-Derived Suppressor Cells in the Peripheral Blood of Cancer Patients Contain a Subset of Immature Neutrophils with Impaired Migratory Properties. Journal of Leukocyte Biology, 89, 311-317. [Google Scholar] [CrossRef] [PubMed]
[27] Lang, S., Bruderek, K., Kaspar, C., Höing, B., Kanaan, O., Dominas, N., et al. (2018) Clinical Relevance and Suppressive Capacity of Human Myeloid-Derived Suppressor Cell Subsets. Clinical Cancer Research, 24, 4834-4844. [Google Scholar] [CrossRef] [PubMed]
[28] Lakschevitz, F.S., Hassanpour, S., Rubin, A., Fine, N., Sun, C. and Glogauer, M. (2016) Identification of Neutrophil Surface Marker Changes in Health and Inflammation Using High-Throughput Screening Flow Cytometry. Experimental Cell Research, 342, 200-209. [Google Scholar] [CrossRef] [PubMed]
[29] Li, S., Cong, X., Gao, H., Lan, X., Li, Z., Wang, W., et al. (2019) Tumor-Associated Neutrophils Induce EMT by Il-17a to Promote Migration and Invasion in Gastric Cancer Cells. Journal of Experimental & Clinical Cancer Research, 38, Article No. 6. [Google Scholar] [CrossRef] [PubMed]
[30] Quaas, A., Pamuk, A., Klein, S., Quantius, J., Rehkaemper, J., Barutcu, A.G., et al. (2021) Sex-Specific Prognostic Effect of CD66b-Positive Tumor-Infiltrating Neutrophils (TANs) in Gastric and Esophageal Adenocarcinoma. Gastric Cancer, 24, 1213-1226. [Google Scholar] [CrossRef] [PubMed]
[31] Chen, Q., Yin, H., Liu, S., Shoucair, S., Ding, N., Ji, Y., et al. (2022) Prognostic Value of Tumor-Associated N1/N2 Neutrophil Plasticity in Patients Following Radical Resection of Pancreas Ductal Adenocarcinoma. Journal for ImmunoTherapy of Cancer, 10, e005798. [Google Scholar] [CrossRef] [PubMed]
[32] Nawaz, A., Bilal, M., Fujisaka, S., Kado, T., Aslam, M.R., Ahmed, S., et al. (2022) Depletion of CD206+ M2-Like Macrophages Induces Fibro-Adipogenic Progenitors Activation and Muscle Regeneration. Nature Communications, 13, Article No. 7058. [Google Scholar] [CrossRef] [PubMed]
[33] Modak, M., Mattes, A., Reiss, D., Skronska-Wasek, W., Langlois, R., Sabarth, N., et al. (2022) CD206+ Tumor-Associated Macrophages Cross-Present Tumor Antigen and Drive Antitumor Immunity. JCI Insight, 7, e155022.
[34] Mishalian, I., Bayuh, R., Eruslanov, E., Michaeli, J., Levy, L., Zolotarov, L., et al. (2014) Neutrophils Recruit Regulatory T‐Cells into Tumors via Secretion of CCL17—A New Mechanism of Impaired Antitumor Immunity. International Journal of Cancer, 135, 1178-1186. [Google Scholar] [CrossRef] [PubMed]
[35] Demers, M., Krause, D.S., Schatzberg, D., Martinod, K., Voorhees, J.R., Fuchs, T.A., et al. (2012) Cancers Predispose Neutrophils to Release Extracellular DNA Traps That Contribute to Cancer-Associated Thrombosis. Proceedings of the National Academy of Sciences, 109, 13076-13081. [Google Scholar] [CrossRef] [PubMed]

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