Department of Virology and Immunology, Institute of Microbiology and Biotechnology, Maria Curie-Skłodowska University, Akademicka 19, 20-033, Lublin, Poland.
Arch Immunol Ther Exp (Warsz). 2018 Apr;66(2):97-111. doi: 10.1007/s00005-017-0480-8. Epub 2017 Jun 28.
It is well known that the microenvironment of solid tumors is rich in inflammatory cells that influence tumor growth and development. Macrophages, called tumor-associated macrophages (TAMs), are the most abundant immune cell population present in tumor tissue. Several studies have demonstrated that the density of TAMs is associated with a poor prognosis and positively correlates with tumor growth. Several studies have proved that TAMs may activate and protect tumor stem cells, stimulate their proliferation as well as promote angiogenesis and metastasis. Furthermore, TAMs-derived cytokines and other proteins, such as CCL-17, CCL-22, TGF-β, IL-10, arginase 1, and galectin-3, make a significant contribution to immunosuppression. Since TAMs influence various aspects of cancer progression, there are many attempts to use them as a target for immunotherapy. The numerous studies have shown that the primary tumor growth and the number of metastatic sites can be significantly decreased by decreasing the population of macrophages in tumor tissue, for example, by blocking recruitment of monocytes or eliminating TAMs already present in the tumor tissue. Moreover, there are attempts at reprogramming TAMs into proinflammatory M1 macrophages or neutralizing the protumoral products of TAMs. Another approach uses TAMs for anticancer drug delivery into the tumor environment. In this review, we would like to summarize the clinical and preclinical trials that were focused on macrophages as a target for anticancer therapies.
众所周知,实体瘤的微环境富含影响肿瘤生长和发展的炎症细胞。巨噬细胞,称为肿瘤相关巨噬细胞(TAMs),是肿瘤组织中最丰富的免疫细胞群体。多项研究表明,TAMs 的密度与预后不良相关,并与肿瘤生长呈正相关。多项研究证明,TAMs 可能激活和保护肿瘤干细胞,刺激其增殖,并促进血管生成和转移。此外,TAMs 衍生的细胞因子和其他蛋白质,如 CCL-17、CCL-22、TGF-β、IL-10、精氨酸酶 1 和半乳糖凝集素-3,对免疫抑制有重要贡献。由于 TAMs 影响癌症进展的各个方面,因此有许多尝试将其作为免疫治疗的靶点。许多研究表明,通过减少肿瘤组织中巨噬细胞的数量,例如通过阻断单核细胞的募集或消除肿瘤组织中已经存在的 TAMs,可以显著降低原发性肿瘤生长和转移部位的数量。此外,还有尝试将 TAMs 重编程为促炎 M1 巨噬细胞或中和 TAMs 的促肿瘤产物。另一种方法是利用 TAMs 将抗癌药物递送至肿瘤环境中。在这篇综述中,我们将总结针对巨噬细胞作为抗癌治疗靶点的临床前和临床研究。