Ward P L, Koeppen H K, Hurteau T, Rowley D A, Schreiber H
Department of Pathology, University of Chicago, Illinois 60637.
Cancer Res. 1990 Jul 1;50(13):3851-8.
The rejection of murine UV-induced skin cancers by normal mice is a striking example of powerful immune surveillance of the normal host against malignant cells. In this study, we show that UV-induced regressor tumors regularly grew progressively and killed mice that were depleted of CD8+ T-cells. Depletion of CD4+ T-cells had no effect, suggesting that CD8+ but not CD4+ T-cells were required for this immune surveillance. To determine whether change in major histocompatibility complex (MHC) class I expression was a frequent event that caused low immunogenicity of tumors or facilitated escape from immune destruction, recently isolated murine tumors of varying degrees of immunogenicity, including highly immunogenic UV-induced regressor, less immunogenic UV-induced progressor, and poorly immunogenic spontaneous progressor tumors, were compared. There was no correlation between the ability of a tumor to grow progressively in a normal immunocompetent host and the level of constitutive class I expression or the level of expression induced in vitro by gamma interferon. (Only 1 of more than 20 progressor tumors analyzed showed complete loss of a MHC class I molecule.) Some progressor variants showed loss of a unique tumor-specific cytotoxic T-lymphocyte-defined antigen, consistent with earlier evidence of antigen loss providing a mechanism for tumor escape. However, most of the host-selected progressor variants retained both MHC class I antigens and the unique tumor antigens that we could detect with cytotoxic T-lymphocyte clones, suggesting that mechanisms other than loss of MHC class I or of the unique target antigen may be involved in escape of some tumors from a highly effective CD8-dependent host surveillance.
正常小鼠对鼠类紫外线诱导的皮肤癌的排斥反应，是正常宿主对恶性细胞进行强大免疫监视的一个显著例子。在本研究中，我们发现紫外线诱导的消退性肿瘤通常会逐渐进展，并导致CD8 + T细胞耗竭的小鼠死亡。CD4 + T细胞的耗竭没有影响，这表明这种免疫监视需要CD8 + 而非CD4 + T细胞。为了确定主要组织相容性复合体（MHC）I类表达的变化是否是导致肿瘤免疫原性降低或促进其逃避免疫破坏的常见事件，我们比较了最近分离的不同免疫原性程度的鼠类肿瘤，包括高免疫原性的紫外线诱导的消退性肿瘤、低免疫原性的紫外线诱导的进展性肿瘤以及低免疫原性的自发性进展性肿瘤。肿瘤在正常免疫活性宿主中逐渐生长的能力，与组成性I类表达水平或γ干扰素体外诱导的表达水平之间没有相关性。（在分析的20多个进展性肿瘤中，只有1个显示MHC I类分子完全缺失。）一些进展性变体显示出一种独特的肿瘤特异性细胞毒性T淋巴细胞定义抗原的缺失，这与早期关于抗原缺失为肿瘤逃逸提供机制的证据一致。然而，大多数宿主选择的进展性变体既保留了MHC I类抗原，也保留了我们能用细胞毒性T淋巴细胞克隆检测到的独特肿瘤抗原，这表明除了MHC I类或独特靶抗原的缺失之外，其他机制可能也参与了一些肿瘤从高效的CD8依赖性宿主监视中逃逸的过程。
