Targeting tumor-associated macrophages as an antitumor strategy
Targeting tumor-associated macrophages as an antitumor strategy
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靶向肿瘤相关巨噬细胞作为抗肿瘤策略
DOI：
10.1016/j.bcp.2020.114354
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发表时间：
2021-01-01
影响因子：
5.8
通讯作者：
Shen, Pingping
中科院分区：
文献类型：
--
作者：
Cheng, Nan;Bai, Xuexia;Shen, Pingping
肿瘤相关巨噬细胞（TAM）是肿瘤微环境（TME）中最广泛浸润的免疫细胞。临床上，TAM的数量与多种癌症的不良结局密切相关。TAM的生物学作用复杂多样，包括介导血管生成、促进肿瘤侵袭和转移以及构建免疫抑制微环境。鉴于TAM在肿瘤发展中的这些关键作用，基于TAM的策略是有吸引力的，并用于某些肿瘤治疗，包括抑制血管生成信号传导、阻断免疫检查点和增强巨噬细胞吞噬作用。已经进行了几次开发TAM靶向剂的尝试，以耗尽TAM或重新编程TAM的行为。有些药物在临床试验中单药治疗、与化疗或免疫疗法联合使用显示出良好的疗效。此外，最近通过为巨噬细胞配备CAR分子开发了一种新的基于巨噬细胞的细胞治疗技术。有望突破实体瘤治疗壁垒。尽管TAM相关研究已经取得了积极的抗肿瘤结果，但需要进一步研究以更好地表征TAM，这将有利于进一步建立肿瘤治疗的新策略。本文简要综述了TAM在TME中的作用，并全面介绍了以TAM为基础的最新肿瘤治疗方案。
Tumor-associated macrophages (TAMs) are the most widely infiltrating immune cells in the tumor microenvironment (TME). Clinically, the number of TAMs is closely correlated with poor outcomes in multiple cancers. The biological actions of TAMs are complex and diverse, including mediating angiogenesis, promoting tumor invasion and metastasis, and building an immunosuppressive microenvironment. Given these pivotal roles of TAMs in tumor development, TAM-based strategies are attractive and used in certain tumor therapies, including inhibition of angiogenic signalling, blockade of the immune checkpoint, and macrophage enhancement phagocytosis. Several attempts to develop TAM-targeted agents have been made to deplete TAMs or reprogram the behaviour of TAMs. Some have shown a favourable curative effect in monotherapy, combination with chemotherapy or immunotherapy in clinical trials. Additionally, a new macrophage-based cell therapeutic technology was recently developed by equipping macrophages with CAR molecules. It is expected to break through barriers to solid tumor treatment. Although TAM-related studies have yielded positive antitumor outcomes, further investigations are needed to better characterize TAMs, which will benefit further establishment of novel strategies for tumor therapy. Here, we concisely summarize the functions of TAMs in the TME and comprehensively introduce the latest TAM-based regimens in cancer treatment.