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巨噬细胞——肿瘤治疗中的靶点与工具:来自卵巢癌的启示

英文原题:Macrophages-Target and Tool in Tumor Treatment: Insights from Ovarian Cancer.

查看英文原题

Macrophages-Target and Tool in Tumor Treatment: Insights from Ovarian Cancer.

PubMed 2025/09/30(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

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中文摘要

当前,科学和医学界正致力于开发治疗多种致命疾病(包括各类癌症)的新技术。研究者努力深入理解肿瘤细胞运作的分子和生化机制,近期尤为关注肿瘤微环境中的免疫细胞,这或将为新型免疫疗法的设计带来突破。肿瘤相关巨噬细胞(TAM)在肿瘤中数量丰富,是卵巢癌进展、转移及治疗耐药的重要调节者。它们既能促进恶性肿瘤发展,也可能成为治疗介质,因此已成为下一代免疫疗法研究的重点。作为治疗靶点,可采取多种策略,包括阻断巨噬细胞募集(如CSF-1/CSF-1R抑制剂)、选择性清除部分TAM亚群(如靶向叶酸受体β),或将免疫抑制性的M2样巨噬细胞重新编程为抗肿瘤的M1表型。另一方面,巨噬细胞也可作为治疗工具,例如将其工程化以增强抗肿瘤免疫,开发嵌合抗原受体巨噬细胞(CAR-M),或利用其作为载体,将药物靶向递送至肿瘤微环境。一种尤其创新的策略是巨噬细胞-药物偶联物(MDC),其利用铁结合蛋白转运(TRAIN)机制,实现治疗药物的精准胞内递送,从而增强药效并减少全身毒性。本综述整合了TAM生物学的现有知识,介绍新兴治疗方法,并强调巨噬细胞干预在卵巢癌中的潜力。将巨噬细胞靶向策略与先进免疫治疗平台结合,或可形成新的治疗模式,显著改善卵巢癌及其他实体瘤患者的结局。本研究强调,巨噬细胞应成为癌症治疗领域的重要研究方向。

展开英文摘要原文

Today, science and medicine are striving to develop novel techniques for treating deadly diseases, including a wide range of cancers. Efforts are being made to better understand the molecular and biochemical mechanisms of tumor cell functioning, but a particular emphasis has recently been given to investigating immune cells residing in the tumor microenvironment, which may lead to revolutionary benefits in the design of new immunotherapies. Among these cells, tumor-associated macrophages (TAMs) are highly abundant and act as critical regulators of ovarian cancer progression, metastasis, and resistance to therapy. Their dual nature-as drivers of malignancy and as potential therapeutic mediators-has positioned them at the forefront of research into next-generation immunotherapies. As therapeutic targets, approaches include blocking macrophage recruitment (e. g. , CSF-1/CSF-1R inhibitors), selectively depleting subsets of TAMs (e. g. , via Folate Receptor Beta), or reprogramming immunosuppressive M2-like macrophages toward an anti-tumor M1 phenotype.

On the other hand, macrophages can also serve as a therapeutic tool-they may be engineered to enhance anti-tumor immunity, as exemplified by the development of Chimeric Antigen Receptor Macrophages (CAR-Ms), or leveraged as delivery vehicles for targeted drug transport into the tumor microenvironment. A particularly innovative strategy involves Macrophage-Drug Conjugates (MDCs), which employs the transfer of iron-binding proteins (TRAIN) mechanism for precise intracellular delivery of therapeutic agents, thereby enhancing drug efficacy while minimizing systemic toxicity.

This review integrates current knowledge of TAM biology, highlights emerging therapeutic approaches, and underscores the promise of macrophage-based interventions in ovarian cancer. By integrating macrophage-targeting strategies with advanced immunotherapeutic platforms, novel treatment paradigms may be determined that could substantially improve outcomes for patients with ovarian cancer and other solid tumors.

Our work highlights that macrophages should be a particular area of research interest in the context of cancer treatment.

论文信息

作者
Górczak M、Kiraga Ł
第一作者单位
Center of Cellular Immunotherapies, Warsaw University of Life Sciences, 02-787 Warsaw, Poland.Poland
通讯作者单位
Division of Pharmacology and Toxicology, Department of Preclinical Sciences, Institute of Veterinary Medicine, Warsaw University of Life Sciences, 02-787 Warsaw, Poland.Poland
文献类型
综述
期刊
Cancers2025 Sep 30
原文标识
PubMed 41097709 · DOI 10.3390/cancers17193182