Takabatake Kiyofumi, Tianyan Piao, Arashima Takuma, Chang Anqi, Kawai Hotaka, Eain Htoo Shwe, Soe Yamin, Min Zin Zin, Fujii Masae, Nakano Keisuke, Nagatsuka Hitoshi
Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8525, Japan.
Cancers (Basel). 2025 Aug 25;17(17):2770. doi: 10.3390/cancers17172770.
In the tumor microenvironment, various immune and stromal cells, such as fibroblasts and vascular endothelial cells, contribute to tumor growth and progression by interacting with cancer cells. Tumor-associated macrophages (TAMs) have attracted attention as major players in the tumor microenvironment. The origin of TAMs is believed to be the infiltration of monocytes derived from bone marrow progenitor cells into tumor tissues and their differentiation into macrophages, whereas tissue-resident macrophages derived from yolk sacs have recently been reported. TAMs infiltrating tumor tissues act in a tumor-promoting manner through immunosuppression, angiogenesis, and the promotion of cancer cell invasion. Reflecting the nature of TAMs, increased TAM invasion and TAM-specific gene expression in tumor tissues may be the new biomarkers for cancer. Moreover, new therapeutic strategies targeting TAMs, such as transformation into immunostimulatory macrophages, suppression of TAM infiltration, and promotion of phagocytosis, are being investigated, and many clinical trials are underway. As the origin and function of TAMs are further elucidated, TAM-targeted therapy is expected to become a new option for the immunotherapy of various cancers, including oral cancers.
在肿瘤微环境中，各种免疫细胞和基质细胞，如成纤维细胞和血管内皮细胞，通过与癌细胞相互作用促进肿瘤生长和进展。肿瘤相关巨噬细胞（TAM）作为肿瘤微环境中的主要参与者受到关注。TAM的来源被认为是骨髓祖细胞衍生的单核细胞浸润到肿瘤组织并分化为巨噬细胞，而最近有报道称其来源于卵黄囊的组织驻留巨噬细胞。浸润肿瘤组织的TAM通过免疫抑制、血管生成和促进癌细胞侵袭等方式发挥促肿瘤作用。反映TAM的特性，肿瘤组织中TAM浸润增加和TAM特异性基因表达可能是癌症的新生物标志物。此外，针对TAM的新治疗策略，如转化为免疫刺激巨噬细胞、抑制TAM浸润和促进吞噬作用等正在研究中，并且许多临床试验正在进行。随着TAM的起源和功能进一步阐明，TAM靶向治疗有望成为包括口腔癌在内的各种癌症免疫治疗的新选择。
