实体瘤的免疫忽视
Immunological ignorance of solid tumors.
作者信息
Ochsenbein Adrian F
机构信息
Department of Clinical Research, University of Berne, Murtenstrasse 35, 3010, Berne, Switzerland.
出版信息
Springer Semin Immunopathol. 2005 Jun;27(1):19-35. doi: 10.1007/s00281-004-0192-0. Epub 2005 Jan 27.
Many peripheral solid tumors such as sarcomas and carcinomas express tumor-specific antigens that can serve as targets for immune effector T cells. Nevertheless, the immune surveillance against clinically manifest carcinomas and sarcomas seems relatively inefficient. Naïve cytotoxic T cells are activated exclusively in secondary lymphoid organs including the spleen and lymph nodes. Tumor antigen might be either cross-presented to naïve cytotoxic T cells by professional antigen-presenting cells (pAPC), or presented directly by tumor cells that migrated to secondary lymphoid organs. Direct priming is quite inefficient during early tumor development because metastasis to lymphoid organs is usually limited to advanced stage diseases. Similarly, the process of cross-priming by pAPC seems to depend on relatively large antigen amounts and on maturation stimuli for dendritic cells, and both requirements may be limiting during initial tumorigenesis. Therefore, the immunosurveillance of solid tumors may fail because they are ignored for too long by the immune system. However, these situations may prove promising for the induction of tumor-specific T cell immunity by vaccination, as the T cell repertoire against these antigens has a naïve phenotype and is not yet affected by tolerance mechanisms.
许多外周实体瘤,如肉瘤和癌,表达可作为免疫效应T细胞靶标的肿瘤特异性抗原。然而,针对临床可见的癌和肉瘤的免疫监视似乎相对低效。初始细胞毒性T细胞仅在包括脾脏和淋巴结在内的二级淋巴器官中被激活。肿瘤抗原可能由专职抗原呈递细胞(pAPC)交叉呈递给初始细胞毒性T细胞,或者由迁移至二级淋巴器官的肿瘤细胞直接呈递。在肿瘤早期发展过程中,直接启动相当低效,因为向淋巴器官的转移通常仅限于晚期疾病。同样,pAPC的交叉启动过程似乎依赖于相对大量的抗原以及树突状细胞的成熟刺激,而这两个要求在初始肿瘤发生过程中可能都受到限制。因此,实体瘤的免疫监视可能会失败,因为它们被免疫系统忽视的时间过长。然而,这些情况可能证明通过疫苗接种诱导肿瘤特异性T细胞免疫很有前景,因为针对这些抗原的T细胞库具有初始表型,尚未受到耐受机制的影响。