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以中性粒细胞为靶点进行癌症治疗。

Targeting neutrophils for cancer therapy.

作者信息

Kwak Jeff W, Houghton A McGarry

机构信息

Translational Science and Therapeutics Division and Human Biology Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.

Division of Pulmonary, Critical Care, and Sleep Medicine, University of Washington, Seattle, WA, USA.

出版信息

Nat Rev Drug Discov. 2025 May 15. doi: 10.1038/s41573-025-01210-8.


DOI:10.1038/s41573-025-01210-8
PMID:40374764
Abstract

Neutrophils are among the most abundant immune cell types in the tumour microenvironment and have been associated with poor outcomes across multiple cancer types. Yet despite mounting evidence of their role in tumour progression, therapeutic strategies targeting neutrophils have only recently gained attention and remain limited in scope. This is probably due to the increasing number of distinct neutrophil subtypes identified in cancer and the limited understanding of the mechanisms by which these subsets influence tumour progression and immune evasion. In this Review, we discuss the spectrum of neutrophil subtypes - including those with antitumour activity - and their potential to polarize towards tumour-suppressive phenotypes. We explore the molecular pathways and effector functions by which neutrophils modulate cancer progression, with an emphasis on identifying tractable therapeutic targets. Finally, we examine emerging clinical trials aimed at modulating neutrophil lineages and consider their implications for patient outcomes.

摘要

中性粒细胞是肿瘤微环境中最丰富的免疫细胞类型之一,并且在多种癌症类型中都与不良预后相关。然而,尽管越来越多的证据表明它们在肿瘤进展中发挥作用,但针对中性粒细胞的治疗策略直到最近才受到关注,并且范围仍然有限。这可能是由于在癌症中鉴定出的不同中性粒细胞亚型数量不断增加,以及对这些亚群影响肿瘤进展和免疫逃逸机制的了解有限。在本综述中,我们讨论了中性粒细胞亚型的范围——包括那些具有抗肿瘤活性的亚型——以及它们向肿瘤抑制表型极化的潜力。我们探索中性粒细胞调节癌症进展的分子途径和效应功能,重点是确定易于处理的治疗靶点。最后,我们研究旨在调节中性粒细胞谱系的新兴临床试验,并考虑它们对患者预后的影响。

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本文引用的文献

[1]
Neutrophils Mediate Protection Against Colitis and Carcinogenesis by Controlling Bacterial Invasion and IL22 Production by γδ T Cells.

Cancer Immunol Res. 2024-4-2

[2]
Neutrophil Elastase: A Key Factor in the Development of Aortic Aneurysm.

Am J Hypertens. 2024-4-15

[3]
Human Tumor-Associated Macrophages and Neutrophils Regulate Antitumor Antibody Efficacy through Lethal and Sublethal Trogocytosis.

Cancer Res. 2024-4-1

[4]
Deterministic reprogramming of neutrophils within tumors.

Science. 2024-1-12

[5]
Interferon-stimulated neutrophils as a predictor of immunotherapy response.

Cancer Cell. 2024-2-12

[6]
Prognostic significance and immunological role of HPRT1 in human cancers.

Biomol Biomed. 2024-3-11

[7]
Human and mouse neutrophils share core transcriptional programs in both homeostatic and inflamed contexts.

Nat Commun. 2023-12-8

[8]
Targeting myeloid chemotaxis to reverse prostate cancer therapy resistance.

Nature. 2023-11

[9]
CD300ld on neutrophils is required for tumour-driven immune suppression.

Nature. 2023-9

[10]
A Phase II Trial of the CD40 Agonistic Antibody Sotigalimab (APX005M) in Combination with Nivolumab in Subjects with Metastatic Melanoma with Confirmed Disease Progression on Anti-PD-1 Therapy.

Clin Cancer Res. 2024-1-5

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