花生四烯酸代谢通路重塑肿瘤免疫微环境的研究进展

doi:10.3969/j.issn.1674-8115.2026.04.012

上海交通大学学报（医学版） ›› 2026, Vol. 46 ›› Issue (4): 521-528.doi: 10.3969/j.issn.1674-8115.2026.04.012

• 综述 • 上一篇

花生四烯酸代谢通路重塑肿瘤免疫微环境的研究进展

缪可言¹, 贾浩², 杨溪¹()

^1.上海交通大学附属第九人民医院口腔颌面-头颈肿瘤科，上海交通大学口腔医学院，国家口腔医学中心，国家口腔疾病临床研究中心，上海市口腔医学重点实验室，上海市口腔医学研究所，上海 200011
^2.上海交通大学基础医学院生物化学与分子细胞生物学系，上海市肿瘤微环境与炎症重点实验室，上海 201318

收稿日期:2025-05-20 接受日期:2025-06-25 出版日期:2026-04-28 发布日期:2026-04-28
通讯作者: 杨溪，主任医师，副教授，博士；电子信箱：yangxi16@163.com。
基金资助:
国家自然科学基金(82272831)

Arachidonic acid metabolism in tumor immune microenvironment remodeling

Miao Keyan¹, Jia Hao², Yang Xi¹()

^1.Department of Oral Maxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology, Shanghai 200011, China
^2.Department of Biochemistry & Molecular Cellular Biology, Shanghai Jiao Tong University College of Basic Medical Sciences; Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai 201318, China

Received:2025-05-20 Accepted:2025-06-25 Online:2026-04-28 Published:2026-04-28
Contact: Yang Xi, E-mail: yangxi16@163.com.
Supported by:
National Natural Science Foundation of China(82272831)

摘要/Abstract

摘要：

肿瘤微环境（tumor microenvironment，TME）是影响肿瘤发生和发展的重要因素，其具有复杂性和动态性，在肿瘤转移过程中扮演着关键角色。花生四烯酸（arachidonic acid，AA）作为一种重要的多不饱和脂肪酸，其代谢产物不仅参与炎症反应和组织稳态维持，更在TME中通过调控免疫细胞的分布、极化、活性与功能状态，深度影响肿瘤的发生、进展及治疗响应。近年来，多项研究发现AA代谢物可通过多种受体作用于各类免疫细胞，重塑免疫微环境，影响肿瘤免疫逃逸和治疗耐受。然而，目前关于AA代谢在TME重塑及肿瘤发生与发展中的具体机制仍未完全阐明。该综述系统阐述AA代谢产物与主要免疫细胞之间的相互作用机制，梳理其在肿瘤免疫调控中的功能特征，重点探讨相关代谢途径在TME重塑中的关键作用，并总结AA代谢靶向策略在肿瘤免疫治疗中的应用研究与进展。深入了解AA代谢与免疫系统之间的动态调控关系，可为开发更精准、个体化的抗肿瘤免疫干预手段提供理论基础与转化依据。

关键词: 花生四烯酸代谢, 肿瘤微环境, 免疫细胞

Abstract:

The tumor microenvironment (TME) constitutes a pivotal component in tumorigenesis and progression, with its inherent complexity and dynamic nature playing a central role in metastatic dissemination. Arachidonic acid (AA), a key polyunsaturated fatty acid, produces metabolites that not only orchestrate inflammatory responses and maintain tissue homeostasis but also profoundly influence tumor initiation, progression, and therapeutic response within the TME by modulating the distribution, polarization, activation, and functional states of immune cells. Recent studies have revealed that these lipid mediators act on diverse immune cell types via distinct receptor pathways, thereby remodeling the immune microenvironment and impacting immune evasion and therapeutic resistance. Despite accumulating insights, the precise mechanisms by which AA metabolism reprograms the TME and contributes to tumor development remain incompletely understood. This review systematically elaborates on the molecular interplay between AA metabolites and major immune cells, outlines their functional characteristics in tumor immune regulation, focuses on the key roles of related metabolic pathways in TME remodeling, and summarizes the research advances and applications of AA metabolism-targeting strategies in tumor immunotherapy. An in-depth understanding of the dynamic crosstalk between AA metabolism and the immune system may provide a conceptual framework for the development of more precise and personalized immunotherapeutic interventions.

Key words: arachidonic acid metabolism, tumor microenvironment (TME), immune cell

中图分类号:

R392.1

缪可言, 贾浩, 杨溪. 花生四烯酸代谢通路重塑肿瘤免疫微环境的研究进展[J]. 上海交通大学学报（医学版）, 2026, 46(4): 521-528.

Miao Keyan, Jia Hao, Yang Xi. Arachidonic acid metabolism in tumor immune microenvironment remodeling[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2026, 46(4): 521-528.

图/表 1

图1 AA代谢通路重塑TME的机制示意图Note： PLA2—phospholipase A2; COX—cyclooxygenase; PGH2—prostaglandin H2; PGG2—prostaglandin G2; PGs—prostaglandins; 5-LOX—5-lipoxygenase; 12,15-LOX—12,15-lipoxygenase; CYP450—cytochrome P450; HpETE—hydroperoxyeicosatetraenoic acid; HETE—hydroxyeicosatetraenoic acid; EET—epoxyeicosatrienoic acid; LTA4—leukotriene A4; LTs—leukotrienes; LTB4—leukotriene B4; LXA4—lipoxin A4; EP2—prostaglandin E receptor 2; EP4—prostaglandin E receptor 4; BLT1—leukotriene B4 receptor 1; FPR2—formyl peptide receptor 2; ALX—lipoxin A4 receptor; IRF4—interferon regulatory factor 4; TAM—tumor-associated macrophage; DC—dendritic cell; NK cell—natural killer cell; M1—classically activated macrophage; M2—alternatively activated macrophage; ARG1—arginase 1; iNOS—inducible nitric oxide synthase; CD206—mannose receptor C-type 1; PD-L1—programmed death-ligand 1; MHC Ⅱ—major histocompatibility complex class Ⅱ; NK1R—neurokinin-1 receptor; CCL5—C-C motif chemokine ligand 5; MMP9—matrix metalloproteinase 9; VEGF—vascular endothelial growth factor; CXCL1—C-X-C motif chemokine ligand 1; CXCL2—C-X-C motif chemokine ligand 2; cAMP—cyclic adenosine monophosphate; PKA—protein kinase A; CREB—cAMP response element-binding protein; NF-κB—nuclear factor κB; MAPK/ERK—mitogen-activated protein kinase/extracellular signal-regulated kinase; PD-1—programmed cell death protein 1; TIM-3—T-cell immunoglobulin and mucin-domain containing-3; Foxp3—forkhead box P3; Treg—regulatory T cell; IgM—immunoglobulin M; IgG—immunoglobulin G; PGE2—prostaglandin E2; IL-10—interleukin 10; XCL1—X-C motif chemokine ligand 1; N2—N2 neutrophil.

Fig 1 Schematic diagram of the mechanisms by which the AA metabolic pathway remodels the TME

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花生四烯酸代谢通路重塑肿瘤免疫微环境的研究进展

Arachidonic acid metabolism in tumor immune microenvironment remodeling

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