Lin Y, Patek P Q, Collins J L, Cohn M
J Natl Cancer Inst. 1985 May;74(5):1025-30.
The immune surveillance hypothesis suggests that cancer evolves as a multistage process. Further, it predicts that cells intermediate on the pathway to cancer are susceptible to host protective mechanisms, and only those variants that are able to escape the protective mechanisms are able to grow as tumors. We have isolated, as lineages, fibroblast lines that express phenotypes predicted by the surveillance hypothesis. The lineages were derived by treating nontransformed cells (N-cells) with chemical carcinogens and by isolating transformed variants in vitro. From the transformants that are tumorigenic in immune-depressed ATXFL mice but rejected by normal mice (I-cells), variants were selected in vivo that had escaped the rejection mechanism(s) and had grown as tumors in normal mice (C-cells). Thus lineages were established comprised of sequentially derived cell lines with the following phenotypes: nontransformed, transformed but susceptible to host protective mechanisms, transformed and resistant to host protective mechanisms (i.e., N----I----C). With the use of in vivo cross-protection experiments, two independently derived I-cell lines were shown to express non-cross-reactive antigens that are not expressed by the parental nontransformed N-cells (i.e., transformation-associated antigens). The transformation-associated antigens are expressed at an equivalent level on the cells that are susceptible to rejection (i.e., I-lines) and those that have escaped rejection (i.e., C-lines). In addition, although the transformation-associated antigens expressed by I-cells induce an effective immune response capable of rejecting both the I-line and C-line, the expression of these antigens on C-cells does not induce an effective immune response. The role of host defense mechanisms in the rejection of these chemically transformed I-cells and the possible mechanisms by which C-cells escape rejection are discussed.
免疫监视假说认为，癌症的发生发展是一个多阶段过程。此外，该假说预测，癌症发展途径中的中间细胞易受宿主保护机制的影响，只有那些能够逃避保护机制的变体才能作为肿瘤生长。我们已分离出成纤维细胞系，作为谱系，它们表达了监视假说所预测的表型。这些谱系是通过用化学致癌物处理未转化细胞（N细胞）并在体外分离转化变体而获得的。从在免疫抑制的ATXFL小鼠中具有致瘤性但被正常小鼠排斥的转化体（I细胞）中，在体内选择出已逃避排斥机制并在正常小鼠中作为肿瘤生长的变体（C细胞）。因此，建立了由具有以下表型的顺序衍生细胞系组成的谱系：未转化、转化但易受宿主保护机制影响、转化且对宿主保护机制有抗性（即N→I→C）。通过体内交叉保护实验，两个独立衍生的I细胞系被证明表达亲本未转化N细胞不表达的非交叉反应性抗原（即转化相关抗原）。转化相关抗原在易被排斥的细胞（即I系）和已逃避排斥的细胞（即C系）上以同等水平表达。此外，尽管I细胞表达的转化相关抗原能诱导一种有效的免疫反应，能够排斥I系和C系，但这些抗原在C细胞上的表达不会诱导有效的免疫反应。本文讨论了宿主防御机制在排斥这些化学转化的I细胞中的作用以及C细胞逃避排斥的可能机制。
