中药调控免疫细胞治疗肝细胞癌的研究进展

龙丽娟; 王宗玉; 赵雅丽; 覃川福; 邱华

doi:10.12449/JCH250223

中药调控免疫细胞治疗肝细胞癌的研究进展

DOI: 10.12449/JCH250223

1.
广西医科大学第一临床医学院，南宁 530021
2.
广西医科大学附属肿瘤医院中医科，南宁 530021
3.
广西医科大学肿瘤医学院，南宁 530021

基金项目:

国家自然科学基金 (81860889);

广西自然科学基金区域高发疾病研究联合专项资助 (2024GXNSFAA010131);

广西自然科学基金区域高发疾病研究联合专项资助 (2024GXNSFBA010182);

广西壮族自治区蛇资源抗肿瘤药用研发与应用工程研究中心项目 (Gui Development and Reform High Technology Letter［2023］No.2727)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：龙丽娟负责课题设计，资料分析，撰写论文；王宗玉、赵雅丽、覃川福参与收集数据，修改论文；邱华负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
邱华， qiuhua8899@163.com （ORCID： 0000-0001-7297-7214）

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出版历程
- 收稿日期: 2024-05-30
- 录用日期: 2024-07-17
- 出版日期: 2025-02-25

Research advances in traditional Chinese medicine for the treatment of hepatocellular carcinoma by regulating immune cells

1.
The First Clinical Medical College of Guangxi Medical University，Nanning 530021，China
2.
Department of Traditional Chinese Medicine，Guangxi Medical University Cancer Hospital，Nanning 530021，China
3.
School of Oncology，Guangxi Medical University，Nanning 530021，China

Research funding:

National Natural Science Foundation of China (81860889);

Joint Project on Regional High-Incidence Diseases Research of Guangxi Natural Science Foundation (2024GXNSFAA010131);

Joint Project on Regional High-Incidence Diseases Research of Guangxi Natural Science Foundation (2024GXNSFBA010182);

Guangxi Zhuang Autonomous Region Snake Resources Anti Tumor Medicinal Research and Application Engineering Research Center Project (Gui Development and Reform High Technology Letter［2023］No.2727)

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Corresponding author: QIU Hua， qiuhua8899@163.com （ORCID： 0000-0001-7297-7214）

摘要

摘要: 肝细胞癌（HCC）是一种常见且死亡率较高的恶性肿瘤，其起病隐匿，病理机制复杂。在肿瘤微环境中，促肿瘤免疫细胞保护肿瘤细胞免受免疫攻击，抗肿瘤免疫细胞发生功能障碍使免疫反应被抑制，最终导致癌症持续恶化。近年来中医药在治疗HCC方面显示出良好的疗效，中药能够调控免疫细胞进而抑制癌细胞增殖与转移。本文通过分析汇总近年来国内外相关文献，总结免疫细胞如何通过免疫抑制途径影响HCC进展以及中药如何调控免疫细胞发挥抗HCC作用，以期为HCC治疗的优化提供理论依据与参考。
- 癌，肝细胞 /
- 免疫细胞 /
- 免疫抑制 /
- 中药
Abstract: Hepatocellular carcinoma （HCC） is a common malignant tumor with a high mortality rate， an insidious onset， and complex pathological mechanisms. In the tumor microenvironment， tumor-promoting immune cells protect tumor cells from immune attacks， while dysfunction of anti-tumor immune cells causes the inhibition of immune response， thereby leading to the continuous deterioration of cancer. In recent years， traditional Chinese medicine has shown good efficacy in the treatment of HCC， and it can inhibit the proliferation and metastasis of cancer cells by regulating immune cells. By analyzing related articles in China and globally， this article summarizes how immune cells affect the progression of HCC through the immunosuppressive pathway and how traditional Chinese medicine exerts an anti-HCC effect by regulating immune cells， in order to provide theoretical basis and reference for optimizing the treatment of HCC.
- Carcinoma， Hepatocellular /
- Immune Cells /
- Immunosuppression /
- Traditional Chinese Drugs

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注： VEGF，血管内皮生长因子；PGE2，前列腺素E2。

图 1 HCC中免疫细胞调控网络

Figure 1. Immune cell regulatory networks in HCC

下载: 全尺寸图片幻灯片

图 2 中药调控免疫细胞治疗HCC的机制

Figure 2. Mechanism of modulating immune cells in HCC treatment by traditional Chinese medicine

下载: 全尺寸图片幻灯片

表 1 中药有效成分或单体调控免疫细胞治疗HCC的机制

Table 1. Mechanism of modulating immune cells in HCC treatment by effective components of traditional Chinese medicine

免疫细胞	有效成分或单体	机制
TAM	青藤碱^［34］	下调α7nAChR表达，抑制M2极化，促进M1极化
	岩黄连总生物碱^［35］	负调控PI3K/AKT/mTOR信号通路，抑制巨噬细胞M2型极化
	隐丹参酮^［36］	调控TLR7/MyD88/NF-κB信号通路，促进巨噬细胞向M1型极化
Treg	雪上一枝蒿多糖组分XP-10^［38］	下调Treg比例
Treg	龙葵碱^［39］	降低Treg含量
MDSC	姜黄素^［42］	减少G-CSF、GM-CSF的分泌及抑制TLR4/NF-κB介导的炎症反应，抑制MDSC的作用
NK细胞	白桦多糖^［46］	增强NK细胞的细胞毒性，增加NK细胞百分比
	五味子素b^［47］	调控穿孔素-颗粒酶B-caspase 3-GSDME通路，介导HepG2细胞焦亡
	蟾毒灵^［48］	降低ADADM9表达，抑制MICA脱落
	附子^［49］	增加NK细胞百分比和CD107a的表达，下调抑制性受体NKp46、NKG2D和TIGIT的表达
CD8⁺ T淋巴细胞	芒柄花黄素^［51］	阻断PD-1/PD-L1通路，激活CD8⁺ T淋巴细胞
	柳穿鱼黄^［52］	增加CD8⁺ T淋巴细胞数量，提高IFN-γ、颗粒酶B等细胞因子及趋化因子CXCL10及其受体CXCR3表达
	芍药苷^［53］	通过SOCS3/STAT3信号通路降低PD-L1表达，增强T淋巴细胞介导的抗肿瘤免疫反应
DC	胀果甘草多糖^［56］	上调DC的表达水平，增加IL-12和IFN-γ含量，降低IL-10和IL-4含量
DC	枸杞多糖LBP3^［57］	抑制IRElα-XBP1通路，改善内质网应激，减少细胞内脂质积累，改善TDC刺激T淋巴细胞的功能

下载: 导出CSV

表 2 中药复方调控免疫细胞治疗HCC的机制

Table 2. Mechanism of modulating immune cells in HCC treatment by traditional Chinese medicine compound

免疫细胞	中药复方	组成	机制
TAM	散结片^［37］	白鲜皮、海藻、白附子、牛黄等	通过抑制MAPK/JNK信号通路，抑制巨噬细胞向M2型极化，促进M1型极化
Treg	大黄蛰虫丸^［40］	大黄、土蝗、水蛭、蝗虫、蛴螬、桃仁、干漆、黄芩、白芍、杏仁、地黄、甘草	通过影响肝癌细胞的代谢、改善肿瘤微环境酸度和谷氨酰胺耗竭或者调控TGF-β/Smad通路来抑制Treg分化
Treg	QHF复方^［41］	华蟾素、人参皂苷、三七总皂苷、香菇多糖	通过调节CCL20/CCR6信号轴，减少Treg肿瘤浸润
MDSC	金猫解毒方^［43］	猫人参、石见穿、山慈菇、鸡内金	阻断CXCL2-CXCR2-ERK和CXCL2-CXCR2-AKT通路，抑制活化的肝星状细胞诱导的MDSC募集和分化
	健脾化瘀汤^［44］	柑橘、姜黄、苍术、黄槐、狼苜蓿	促进MDSC分化，减少MDSC中ROS的表达，降低对CD4⁺ T淋巴细胞的抑制作用
	甘遂半夏汤^［45］	甘遂、半夏、白芍、甘草	通过抑制AKT/STAT3/ERK信号通路，下调IL-1β和IFN-γ的表达，减少MDSC的积累
NK细胞	玉屏风散^［50］	黄芪、白术、防风	抑制STAT3/p-STAT3、PD-L1的蛋白表达，以及IDO、TGF-β的分泌，促进颗粒酶B、穿孔素、IFN-γ的表达
CD8⁺ T淋巴细胞	加味当归贝母苦参丸^［54］	当归、贝母、苦参、山慈菇、全蝎、黄芪	促进CD8⁺T淋巴细胞的增殖，降低LAG-3表达
CD8⁺ T淋巴细胞	养阴扶正解毒方^［55］	北沙参、麦冬、黄芪、白术、柴胡、苦参、徐长卿、白花蛇舌草	升高CD8⁺ T淋巴细胞的比例，改善抑制受体的过表达，降低炎症和免疫抑制细胞因子水平，提高效应细胞因子水平，调节T淋巴细胞转录
DC	鳖龙软肝汤^［58］	桃仁、莪术、鳖甲、地龙、茯苓、柴胡、白芍、甘草	促进外周血DC的增殖
DC	玉屏风颗粒^［59］	黄芪、白术、防风	调控TSLP-OX40L通路促进DC的成熟

下载: 导出CSV

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