Klein G, Klein E
Proc Natl Acad Sci U S A. 1977 May;74(5):2121-5. doi: 10.1073/pnas.74.5.2121.
Spontaneous tumours are defined as tumors that develop in the absence of all experimental interference. In contrast to the widely documented, strong rejection reactions against most virus-induced tumors, spontaneous tumors evoke little or no detectable rejection reaction in intact or preimmunized syngeneic hosts. The difference can be viewed in relation to the contrasting natural history of the two conditions. Spontaneous tumors evolve in several steps, as a fule. "Tumor progression" is a microevolutionary process at the level of the somatic tissue where successive clonal variants replace each other. Each new variant gains the upper hand due to its greater independence of some restricting host mechanism. Independence of immune restrictions must be part of this process. Host selection for immune resistance apparently plays no major role here, presumably because most of the naturally occurring tumors arise after the host has passed the peak of its reproductive period. Protection against the oncogenic effects of ubiquitous tumor viruses is, on the other hand, the result of host selection for immune mechanisms favoring prompt rejection of virus-transformed cells. This is neither synonymous with nor related to protection against the viral infection per se, which is frequently successful and usually quite harmless. A certain relationship can be perceived between the degree of viral ubiquity and the strength of immune protection against the corresponding tumor cells. Natural selection for host recognition of commonly occurring, virally induced changes in neoplastic cell membranes can be surmised to occur, at least in part, by the fixation of appropriate immune responsiveness (Ir) genes. The role of Ir genes for tumor recognition can be approached by the genetic analysis of the F1 hybrid resistance effect. Unresponsiveness to spontaneous tumors may be overcome by target-cell modification, e.g., by chemical coupling, somatic cell hybridization, or viral "xenogenization".
自发性肿瘤被定义为在没有任何实验干预的情况下发生的肿瘤。与针对大多数病毒诱导肿瘤的广泛记录的强烈排斥反应形成对比的是，自发性肿瘤在完整或预先免疫的同基因宿主中几乎不会引发或引发几乎无法检测到的排斥反应。这种差异可以从两种情况截然不同的自然史角度来看待。自发性肿瘤通常会分几个步骤演变。“肿瘤进展”是体细胞组织水平上的一个微观进化过程，在此过程中连续的克隆变体相互取代。每个新变体由于对某些限制宿主机制的更大独立性而占据上风。免疫限制的独立性必然是这个过程的一部分。宿主对免疫抗性的选择显然在这里不起主要作用，大概是因为大多数自然发生的肿瘤是在宿主度过其生殖期高峰之后出现的。另一方面，针对普遍存在的肿瘤病毒致癌作用的保护是宿主选择有利于迅速排斥病毒转化细胞的免疫机制的结果。这既不等同于针对病毒感染本身的保护，也与之无关，病毒感染通常是成功的且通常相当无害。可以察觉到病毒普遍程度与针对相应肿瘤细胞的免疫保护强度之间存在一定关系。可以推测，至少部分是通过固定适当的免疫反应性（Ir）基因，宿主对肿瘤细胞膜中常见的病毒诱导变化的识别进行自然选择。对自发性肿瘤的无反应性可以通过靶细胞修饰来克服，例如通过化学偶联、体细胞杂交或病毒“异种源化”。
