Role of Macrophage Ferroptosis in Immune Evasion of Hepatocellular Carcinoma and Research Progress on Traditional Chinese Medicine Intervention

PENG Jinxiang; LI Xiaojuan; LU Man; XU Xinhua; SHU Mengxian; WU Feng

doi:10.3971/j.issn.1000-8578.2026.25.0926

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Role of Macrophage Ferroptosis in Immune Evasion of Hepatocellular Carcinoma and Research Progress on Traditional Chinese Medicine Intervention

更新时间：2026-11-05

- Role of Macrophage Ferroptosis in Immune Evasion of Hepatocellular Carcinoma and Research Progress on Traditional Chinese Medicine Intervention
- Vol. 53, Issue 4, Pages: 316-324(2026)
- 作者机构：
  
  1. 湖北恩施学院医学部,恩施,445000
  2. 湖北中医药大学中医学院,武汉,430065
  3. 湖北时珍实验室,武汉,430060
  4. 恩施土家族苗族自治州中心医院肺病糖尿病科,恩施,445000
- 作者简介：
- 基金信息：
- DOI：10.3971/j.issn.1000-8578.2026.25.0926
  CLC： R735.7
- Published：2026
- 稿件说明：
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彭金香, 李晓娟, 卢曼, 徐新华, 舒孟仙, 吴沣. 肿瘤相关巨噬细胞铁死亡在肝细胞癌免疫逃逸中的作用及中医药调控研究进展[J]. 肿瘤防治研究, 2026, 53(4): 316-324.

PENG Jinxiang, LI Xiaojuan, LU Man, et al. Role of Macrophage Ferroptosis in Immune Evasion of Hepatocellular Carcinoma and Research Progress on Traditional Chinese Medicine Intervention[J]. 2026, 53(4): 316-324.
彭金香, 李晓娟, 卢曼, 徐新华, 舒孟仙, 吴沣. 肿瘤相关巨噬细胞铁死亡在肝细胞癌免疫逃逸中的作用及中医药调控研究进展[J]. 肿瘤防治研究, 2026, 53(4): 316-324. DOI： 10.3971/j.issn.1000-8578.2026.25.0926.

PENG Jinxiang, LI Xiaojuan, LU Man, et al. Role of Macrophage Ferroptosis in Immune Evasion of Hepatocellular Carcinoma and Research Progress on Traditional Chinese Medicine Intervention[J]. 2026, 53(4): 316-324. DOI： 10.3971/j.issn.1000-8578.2026.25.0926.

摘要

肝细胞癌（HCC）的高度免疫抑制性肿瘤微环境（TIME）是免疫治疗效果受限的关键。肿瘤相关巨噬细胞（TAMs）向促肿瘤M2型极化是免疫逃逸的主要驱动机制。铁死亡作为一种铁依赖性程序性细胞死亡，与肝脏铁代谢及免疫调控密切相关，为肿瘤干预提供了新靶点。本文系统阐述了TAMs铁死亡在HCC免疫逃逸中的作用机制，重点论述了基于中医药“扶正祛邪”思想的“双向调控”干预策略。该策略一方面通过“祛邪”之法，利用M2型TAMs的代谢脆弱性精准诱导其铁死亡；另一方面通过“扶正”之法，保护M1型TAMs及CD8

T细胞等抗肿瘤免疫细胞免于氧化损伤。这种双向调节模式展现了中医药系统性重塑TIME的独特优势。因此，基于“扶正祛邪”理论精准调控TAMs铁死亡，是突破当前HCC免疫治疗瓶颈极具潜力的中西医结合新策略，其临床转化价值有待进一步验证。

Abstract

Hepatocellular carcinoma (HCC) develops within a profoundly immunosuppressive tumor immune microenvironment (TIME)

which limits the efficacy of immunotherapy. Polarization of tumor-associated macrophages (TAMs) toward a pro-tumorigenic M2 phenotype is a major driver of immune escape. Ferroptosis

an iron-dependent regulated cell death program

intersects with hepatic iron metabolism and immune regulation and thus offers promising points of therapeutic intervention. This review systematically elucidates the mechanistic role of TAM ferroptosis in HCC imm

une evasion and highlights a “bidirectional regulation” intervention strategy grounded in the Traditional Chinese medicine (TCM) principle of “fortifying healthy qi and eliminating pathogens” (Fuzheng Quxie). This strategy employs “eliminating pathogens” (Quxie) approaches to exploit the metabolic vulnerability of M2-like TAMs and precisely induce their ferroptosis. Moreover

it utilizes “fortifying healthy qi” (Fuzheng) approaches to protect M1-like TAMs and CD8

T cells from oxidative damage. This parallel “induction-protection” paradigm demonstrates the unique advantages of TCM in systemically remodeling TIME through multitarget synergistic actions. Accordingly

precision regulation of TAM ferroptosis based on the Fuzheng Quxie theory represents a promising integrative Chinese-Western medicine strategy for overcoming current bottlenecks in HCC immunotherapy

although its clinical translational potential warrants further validation.

关键词

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references

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