Macrophages are critical effectors of antibody therapies for cancer.
Macrophages are critical effectors of antibody therapies for cancer.
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DOI：
10.1080/19420862.2015.1011450
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发表时间：
2015
期刊：
影响因子：
5.3
通讯作者：
Weissman IL
中科院分区：
文献类型：
--
作者：
Weiskopf K;Weissman IL
巨噬细胞是源自循环单核细胞的先天性免疫细胞，存在于所有组织中，并参与许多病理状态。巨噬细胞在癌症中起着双重作用，它们促进肿瘤生长，但也作为治疗性抗体的关键免疫效应物。巨噬细胞表达所有类型的Fcγ受体，并且它们具有通过抗体依赖性吞噬作用破坏肿瘤的巨大潜力。许多研究表明，巨噬细胞吞噬作用是许多批准用于治疗癌症的抗体的主要作用机制。因此，许多增强巨噬细胞对治疗性抗体的反应的方法正在研究中，包括探索新靶点和开发具有增强功能的抗体。例如，CD 47与信号调节蛋白α（SIRPα）的相互作用可作为骨髓特异性免疫检查点，限制巨噬细胞对抗体治疗的反应，而CD 47阻断剂可克服这一障碍，增强吞噬作用。巨噬细胞对抗体疗法的应答也可以用工程化Fc变体、双特异性抗体或抗体-药物缀合物增强。巨噬细胞已被证明是癌症免疫治疗的成功效应物，进一步的研究将释放它们的全部潜力，使患者受益。
Macrophages are innate immune cells that derive from circulating monocytes, reside in all tissues, and participate in many states of pathology. Macrophages play a dichotomous role in cancer, where they promote tumor growth but also serve as critical immune effectors of therapeutic antibodies. Macrophages express all classes of Fcγ receptors, and they have immense potential to destroy tumors via the process of antibody-dependent phagocytosis. A number of studies have demonstrated that macrophage phagocytosis is a major mechanism of action of many antibodies approved to treat cancer. Consequently, a number of approaches to augment macrophage responses to therapeutic antibodies are under investigation, including the exploration of new targets and development of antibodies with enhanced functions. For example, the interaction of CD47 with signal-regulatory protein α (SIRPα) serves as a myeloid-specific immune checkpoint that limits the response of macrophages to antibody therapies, and CD47-blocking agents overcome this barrier to augment phagocytosis. The response of macrophages to antibody therapies can also be enhanced with engineered Fc variants, bispecific antibodies, or antibody-drug conjugates. Macrophages have demonstrated success as effectors of cancer immunotherapy, and further investigation will unlock their full potential for the benefit of patients.