Macrophages as tools and targets in cancer therapy.
Macrophages as tools and targets in cancer therapy.
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巨噬细胞作为肿瘤治疗的工具和靶点
DOI：
10.1038/s41573-022-00520-5
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发表时间：
2022-11
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--
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中科院分区：
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肿瘤相关巨噬细胞是肿瘤微环境的重要组成部分，在血管生成、细胞外基质重塑、癌细胞增殖、转移和免疫抑制，以及对化疗药物和检查点阻断免疫治疗的抵抗中起着重要作用。相反，当适当地激活时，巨噬细胞可以介导癌细胞的吞噬和细胞毒性肿瘤杀伤，并与先天性和获得性免疫系统的组成部分进行有效的双向相互作用。因此，它们已成为癌症治疗的治疗靶点。巨噬细胞靶向策略包括参与促进肿瘤的髓系细胞募集和极化的细胞因子和趋化因子的抑制剂以及它们的抗肿瘤和免疫刺激功能的激活剂。早期临床试验表明，靶向髓系细胞功能的负调控因子(检查点)确实具有抗肿瘤的潜力。最后，鉴于粒单核细胞不断向肿瘤组织募集，随着嵌合抗原受体效应细胞的发展，巨噬细胞成为细胞治疗的候选细胞。以巨噬细胞为中心的治疗策略有可能补充和协同肿瘤学中目前可用的工具。巨噬细胞可以促进肿瘤的形成，增强抗肿瘤的反应。这篇综述讨论了巨噬细胞在肿瘤微环境中重新编程的分子机制，并提供了巨噬细胞靶向治疗癌症的概述。
Tumour-associated macrophages are an essential component of the tumour microenvironment and have a role in the orchestration of angiogenesis, extracellular matrix remodelling, cancer cell proliferation, metastasis and immunosuppression, as well as in resistance to chemotherapeutic agents and checkpoint blockade immunotherapy. Conversely, when appropriately activated, macrophages can mediate phagocytosis of cancer cells and cytotoxic tumour killing, and engage in effective bidirectional interactions with components of the innate and adaptive immune system. Therefore, they have emerged as therapeutic targets in cancer therapy. Macrophage-targeting strategies include inhibitors of cytokines and chemokines involved in the recruitment and polarization of tumour-promoting myeloid cells as well as activators of their antitumorigenic and immunostimulating functions. Early clinical trials suggest that targeting negative regulators (checkpoints) of myeloid cell function indeed has antitumor potential. Finally, given the continuous recruitment of myelomonocytic cells into tumour tissues, macrophages are candidates for cell therapy with the development of chimeric antigen receptor effector cells. Macrophage-centred therapeutic strategies have the potential to complement, and synergize with, currently available tools in the oncology armamentarium. Macrophages can promote tumorigenesis and enhance the antitumour response. This Review discusses the molecular mechanisms underlying the reprogramming of macrophages in the tumour microenvironment and provides an overview of macrophage-targeted therapies for the treatment of cancer.
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