Adaptive immunity maintains occult cancer in an equilibrium state
Adaptive immunity maintains occult cancer in an equilibrium state
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DOI：
10.1038/nature06309
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发表时间：
2007-12-06
期刊：
影响因子：
64.8
通讯作者：
Schreiber, Robert D.
中科院分区：
文献类型：
--
作者：
Koebel, Catherine M.;Vermi, William;Schreiber, Robert D.
免疫控制和塑造癌症的能力，即癌症免疫编辑，是三个过程（1-8）的结果，这些过程独立或顺序（9）发挥作用：（癌症免疫监视，其中免疫功能作为初始宿主的外源性肿瘤抑制因子）;平衡（转化细胞的扩增被免疫抑制）;和逃逸（具有减弱的免疫原性或减弱免疫应答的能力的肿瘤细胞变体生长成临床上明显的癌症）。现在存在广泛的实验支持消除和逃逸过程，因为免疫缺陷小鼠比野生型小鼠发展更多的致癌物诱导和自发性癌症，并且来自免疫缺陷小鼠的肿瘤细胞比来自免疫活性小鼠的肿瘤细胞更具免疫原性。相比之下，平衡过程主要是从临床观察中推断出来的，包括器官供体未检测到的（隐匿性）癌症移植到免疫抑制受体的报告（10）。在此，我们使用小鼠模型的原发性化学致癌作用，并表明，平衡发生，是从消除和逃逸的机械区别，并在平衡中的肿瘤细胞转化，但在体内增殖不良。我们还表明，处于平衡状态的肿瘤细胞是未经编辑的，但当它们自发地逃避免疫控制并生长成临床上明显的肿瘤时，它们就会被编辑。这些结果表明，除了破坏肿瘤细胞和塑造肿瘤免疫原性外，幼稚小鼠的免疫系统还可以长时间抑制癌症生长。
The capacity of immunity to control and shape cancer, that is, cancer immunoediting, is the result of three processes(1-8) that function either independently or in sequence(9): elimination ( cancer immunosurveillance, in which immunity functions as an extrinsic tumour suppressor in naive hosts); equilibrium ( expansion of transformed cells is held in check by immunity); and escape ( tumour cell variants with dampened immunogenicity or the capacity to attenuate immune responses grow into clinically apparent cancers). Extensive experimental support now exists for the elimination and escape processes because immunodeficient mice develop more carcinogen-induced and spontaneous cancers than wild-type mice, and tumour cells from immunodeficient mice are more immunogenic than those from immunocompetent mice. In contrast, the equilibrium process was inferred largely from clinical observations, including reports of transplantation of undetected ( occult) cancer from organ donor into immuno-suppressed recipients(10). Herein we use a mouse model of primary chemical carcinogenesis and demonstrate that equilibrium occurs, is mechanistically distinguishable from elimination and escape, and that neoplastic cells in equilibrium are transformed but proliferate poorly in vivo. We also show that tumour cells in equilibrium are unedited but become edited when they spontaneously escape immune control and grow into clinically apparent tumours. These results reveal that, in addition to destroying tumour cells and sculpting tumour immunogenicity, the immune system of a naive mouse can also restrain cancer growth for extended time periods.