Engelhard V H, Bullock T N, Colella T A, Mullins D W
Department of Microbiology, University of Virginia Health Sciences Center, Charlottesville, USA.
Cancer J. 2000 May;6 Suppl 3:S272-80.
Although the arsenal of a healthy immune system includes both circulating antibodies and cellular components such as T cells, the latter seem to be particularly important in tumor immunology. Under normal conditions, the immune system does not react to the body's cells, which may be described as expressing "self" antigens on the cell surface. When a cell becomes cancerous, however, novel antigens are expressed on the cell surface. These novel "tumor" antigens are recognized as foreign by the body's immune system, and the cells that express them are destroyed or incapacitated. Whereas antibodies may react directly with protein antigens, T cells instead recognize peptide antigens presented by class I and class II molecules of the major histocompatibility complex (MHC). All cells normally break down proteins that they have made. The class I antigen-processing pathway has evolved to display peptides produced by this breakdown process as a way to provide information to cytotoxic T cells about what the cell is making. The display of new peptides as a result of infection or transformation can stimulate cytotoxic T cells to kill the cell. In addition, antigen-processing cells such as dendritic cells engulf dead or dying cells and degradeproteins into peptide fragments. These peptides are then displayed by the MHC class II molecules and presented to T helper cells, which augment the activity of the cytotoxic T cells. Cytotoxic T lymphocytes have recently been isolated from human tumors (especially melanoma) and are critical to the development of promising immunotherapeutic agents. As we shall discuss, these cells can recognize antigens that are common to tumors from different patients. We shall also explore how advances in instrumentation and the use of transgenic mice have increased our understanding of tumor-associated peptides to the point where we can begin to strive for a peptide-based therapeutic vaccine. The caveats for such therapy will also be addressed.
尽管健康免疫系统的武器库包括循环抗体和T细胞等细胞成分，但后者在肿瘤免疫学中似乎尤为重要。在正常情况下，免疫系统不会对身体细胞产生反应，这些细胞可被描述为在细胞表面表达“自身”抗原。然而，当细胞发生癌变时，新的抗原会在细胞表面表达。这些新的“肿瘤”抗原被机体免疫系统识别为外来物，表达它们的细胞会被破坏或失去功能。抗体可能直接与蛋白质抗原发生反应，而T细胞则识别由主要组织相容性复合体（MHC）的I类和II类分子呈递的肽抗原。所有细胞通常都会分解它们所产生的蛋白质。I类抗原加工途径已经进化，以展示由这种分解过程产生的肽，作为向细胞毒性T细胞提供有关细胞正在产生什么的信息的一种方式。感染或转化导致的新肽展示可刺激细胞毒性T细胞杀死该细胞。此外，抗原加工细胞如树突状细胞吞噬死亡或濒死细胞，并将蛋白质降解成肽片段。然后这些肽由MHC II类分子展示并呈递给辅助性T细胞，辅助性T细胞可增强细胞毒性T细胞的活性。细胞毒性T淋巴细胞最近已从人类肿瘤（尤其是黑色素瘤）中分离出来，对有前景的免疫治疗药物的开发至关重要。正如我们将讨论的，这些细胞可以识别不同患者肿瘤共有的抗原。我们还将探讨仪器技术的进步和转基因小鼠的使用如何增进了我们对肿瘤相关肽的理解，使我们能够开始努力研发基于肽的治疗性疫苗。此类治疗的注意事项也将予以讨论。
