Wang Teh-Wei, Nakanishi Makoto
Division of Cancer Cell Biology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Division of Cancer Cell Biology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Trends Cell Biol. 2025 Mar;35(3):248-257. doi: 10.1016/j.tcb.2024.06.007. Epub 2024 Jul 17.
Several lines of evidence suggest that the age-dependent accumulation of senescent cells leads to chronic tissue microinflammation, which in turn contributes to age-related pathologies. In general, senescent cells can be eliminated by the host's innate and adaptive immune surveillance system, including macrophages, NK cells, and T cells. Impaired immune surveillance leads to the accumulation of senescent cells and accelerates the aging process. Recently, senescent cells, like cancer cells, have been shown to express certain types of immune checkpoint proteins as well as non-classical immune-tolerant MHC variants, leading to immune escape from surveillance systems. Thus, immune checkpoint blockade (ICB) may be a promising strategy to enhance immune surveillance of senescence, leading to the amelioration of some age-related diseases and tissue dysfunction.
多条证据表明,衰老细胞随年龄增长而积累会导致慢性组织微炎症,进而促成与年龄相关的病理状况。一般来说,衰老细胞可被宿主的固有和适应性免疫监视系统清除,包括巨噬细胞、自然杀伤细胞和T细胞。免疫监视受损会导致衰老细胞积累并加速衰老进程。最近发现,衰老细胞与癌细胞一样,会表达某些类型的免疫检查点蛋白以及非经典的免疫耐受型主要组织相容性复合体(MHC)变体,从而实现免疫逃逸,逃避监视系统。因此,免疫检查点阻断(ICB)可能是一种有前景的策略,可增强对衰老的免疫监视,从而改善一些与年龄相关的疾病和组织功能障碍。