Xia Yuqiong, Rao Lang, Yao Huimin, Wang Zhongliang, Ning Pengbo, Chen Xiaoyuan
Engineering Research Center of Molecular & Neuroimaging, Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi, 710126, China.
Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.
Adv Mater. 2020 Oct;32(40):e2002054. doi: 10.1002/adma.202002054. Epub 2020 Aug 28.
Macrophages play an important role in cancer development and metastasis. Proinflammatory M1 macrophages can phagocytose tumor cells, while anti-inflammatory M2 macrophages such as tumor-associated macrophages (TAMs) promote tumor growth and invasion. Modulating the tumor immune microenvironment through engineering macrophages is efficacious in tumor therapy. M1 macrophages target cancerous cells and, therefore, can be used as drug carriers for tumor therapy. Herein, the strategies to engineer macrophages for cancer immunotherapy, such as inhibition of macrophage recruitment, depletion of TAMs, reprograming of TAMs, and blocking of the CD47-SIRPα pathway, are discussed. Further, the recent advances in drug delivery using M1 macrophages, macrophage-derived exosomes, and macrophage-membrane-coated nanoparticles are elaborated. Overall, there is still significant room for development in macrophage-mediated immune modulation and macrophage-mediated drug delivery, which will further enhance current tumor therapies against various malignant solid tumors, including drug-resistant tumors and metastatic tumors.
巨噬细胞在癌症发展和转移中发挥着重要作用。促炎性M1巨噬细胞可以吞噬肿瘤细胞,而抗炎性M2巨噬细胞,如肿瘤相关巨噬细胞(TAM),则促进肿瘤生长和侵袭。通过改造巨噬细胞来调节肿瘤免疫微环境在肿瘤治疗中是有效的。M1巨噬细胞靶向癌细胞,因此可用作肿瘤治疗的药物载体。本文讨论了改造巨噬细胞用于癌症免疫治疗的策略,如抑制巨噬细胞募集、清除TAM、对TAM进行重编程以及阻断CD47-SIRPα通路。此外,还阐述了使用M1巨噬细胞、巨噬细胞衍生的外泌体和巨噬细胞膜包被的纳米颗粒进行药物递送的最新进展。总体而言,巨噬细胞介导的免疫调节和巨噬细胞介导的药物递送仍有很大的发展空间,这将进一步增强目前针对各种恶性实体瘤(包括耐药肿瘤和转移性肿瘤)的肿瘤治疗。
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