Stress-induced proteins in immune response to cancer.
Stress-induced proteins in immune response to cancer.
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DOI：
10.1007/978-3-642-75875-1_7
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发表时间：
1991
影响因子：
--
通讯作者：
P. K. Srivastava;Robert G. Maki
中科院分区：
文献类型：
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作者：
P. K. Srivastava;Robert G. Maki
化学诱导的近交系小鼠肿瘤在肿瘤被诱导的动物和相同近交系的其他动物中引起免疫。免疫力对每种肿瘤都是特异性的：即使在一只动物中用相同的致癌物诱发两种肿瘤也不会发生交叉反应。此后，在由许多化学和物理致癌物诱发的肉瘤和癌的情况下，以及在包括小鼠、大鼠和豚鼠在内的几个物种中，观察到了对癌症的免疫力。介导对肿瘤免疫的分子的性质是癌症免疫学中的中心问题。少数这样的分子已经被生物化学定义。其中，一些是在肿瘤细胞中表达的病毒抗原，而另一些与病毒抗原的关系尚不清楚。令人惊讶的是，大多数非病毒肿瘤抗原与应激诱导蛋白具有同源性。四个家庭这样的分子进行了讨论：gp 96（热休克蛋白100）和p84/86（热休克蛋白90）抗原的化学诱导小鼠肉瘤，热休克蛋白70抗原的肿瘤通过转染正常大鼠胎儿成纤维细胞与H-ras癌基因，和白蛋白抗原的小鼠黑色素瘤和大鼠组织细胞瘤。（白蛋白样抗原包括在应激诱导蛋白中，因为白蛋白虽然在成体组织中组成型表达，但在胎儿肝脏中是热休克诱导的。）这些抗原中的每一种都是中等丰度的蛋白质，不仅存在于肿瘤中，而且存在于正常组织中。施用来自肿瘤而不是来自正常组织的这些抗原制剂中的每一种，使得动物对用制备抗原的肿瘤活细胞的攻击具有免疫力。然而，在正常组织和肿瘤之间没有观察到抗原的结构差异。这表明，这些应激诱导的蛋白质本身可能不是肿瘤抗原，但可能是免疫原性部分，如短肽的载体。因此，应激诱导的蛋白质可以作为抗原呈递分子，如MHC编码的分子，或者作为辅助分子，通过MHC分子呈递抗原。应激诱导的蛋白质与包括肽在内的多种分子结合的能力与这种可能性是一致的。
Chemically induced tumors of inbred mice elicit immunity in animals in which the tumors are induced and in other animals of the same inbred stock. The immunity is specific for each tumor: even two tumors induced in one animal with the same carcinogen are not cross-reactive. Immunity to cancer has since been observed in the case of sarcomas and carcinomas induced by a number of chemical and physical carcinogens and in several species, including mice, rats, and guinea pigs. The nature of molecules which mediate immunity to tumors is a central question in cancer immunology. A small number of such molecules have been biochemically defined. Of these, some are viral antigens expressed in tumor cells, while the relationship of some others to viral antigens is unclear. A surprising majority of nonviral tumor antigens have turned out to bear homology with stress-induced proteins. Four families of such molecules are discussed: the gp96 (hsp100) and p84/86 (hsp90) antigens of chemically induced mouse sarcomas, hsp70 antigens of tumors obtained by transfection of normal rat fetal fibroblasts with an H-ras oncogene, and the albuminoid antigens of murine melanomas and a rat histiocytoma.(Albumin-like antigens are included among the stress-induced proteins because albumin, though constitutively expressed in adult tissues, is heat shock inducible in fetal liver.) Each of these antigens is a moderately abundant protein, present not only in tumors but also in normal tissues. Administration of each of these antigen preparations from the tumor, but not from normal tissue, renders the animal immune to challenge with live cells of the tumor from which the antigens are prepared. And yet, no structural differences in the antigens have been observed between normal tissues and tumors. It is suggested that these stress-induced proteins may not be tumor antigens per se, but may be carriers of immunogenic moieties such as short peptides. The stress-induced proteins may therefore serve either as antigen-presenting molecules like the MHC-encoded molecules or as accessory molecules in the presentation of antigens by MHC molecules. The ability of stress-induced proteins to bind to a variety of molecules, including peptides, is consistent with this possibility.