Ngambenjawong Chayanon, Gustafson Heather H, Pun Suzie H
Department of Bioengineering and Molecular Engineering and Sciences Institute, University of Washington, Seattle, WA 98195, United States.
Department of Bioengineering and Molecular Engineering and Sciences Institute, University of Washington, Seattle, WA 98195, United States.
Adv Drug Deliv Rev. 2017 May 15;114:206-221. doi: 10.1016/j.addr.2017.04.010. Epub 2017 Apr 25.
As an essential innate immune population for maintaining body homeostasis and warding off foreign pathogens, macrophages display high plasticity and perform diverse supportive functions specialized to different tissue compartments. Consequently, aberrance in macrophage functions contributes substantially to progression of several diseases including cancer, fibrosis, and diabetes. In the context of cancer, tumor-associated macrophages (TAMs) in tumor microenvironment (TME) typically promote cancer cell proliferation, immunosuppression, and angiogenesis in support of tumor growth and metastasis. Oftentimes, the abundance of TAMs in tumor is correlated with poor disease prognosis. Hence, significant attention has been drawn towards development of cancer immunotherapies targeting these TAMs; either depleting them from tumor, blocking their pro-tumoral functions, or restoring their immunostimulatory/tumoricidal properties. This review aims to introduce readers to various aspects in development and evaluation of TAM-targeted therapeutics in pre-clinical and clinical stages.
作为维持机体稳态和抵御外来病原体的重要先天性免疫细胞群体，巨噬细胞具有高度可塑性，并在不同组织微环境中发挥多种特异性支持功能。因此，巨噬细胞功能异常在包括癌症、纤维化和糖尿病在内的多种疾病进展中起重要作用。在癌症背景下，肿瘤微环境（TME）中的肿瘤相关巨噬细胞（TAM）通常促进癌细胞增殖、免疫抑制和血管生成，以支持肿瘤生长和转移。通常，肿瘤中TAM的丰度与疾病预后不良相关。因此，针对这些TAM的癌症免疫疗法的开发受到了广泛关注；要么从肿瘤中清除它们，阻断其促肿瘤功能，要么恢复其免疫刺激/杀肿瘤特性。本综述旨在向读者介绍临床前和临床阶段TAM靶向治疗药物开发和评估的各个方面。
