Expression of tumour-specific antigens underlies cancer immunoediting.
Expression of tumour-specific antigens underlies cancer immunoediting.
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DOI：
10.1038/nature10803
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发表时间：
2012-02-08
期刊：
影响因子：
64.8
通讯作者：
Jacks, Tyler
中科院分区：
文献类型：
--
作者：
DuPage, Michel;Mazumdar, Claire;Schmidt, Leah M.;Cheung, Ann F.;Jacks, Tyler
癌症免疫编辑是一种免疫细胞，特别是适应性免疫系统的淋巴细胞，通过驱动对免疫攻击敏感性降低的肿瘤细胞的生长来保护宿主免受癌症发展并改变肿瘤进展的过程。致癌物诱导的小鼠癌症模型表明，免疫受损小鼠的原发性肿瘤易感性增强，而相反，移植到野生型小鼠后，这种肿瘤的生长能力降低。然而，关于癌症免疫编辑过程的许多问题仍未得到解答，部分原因是已知的抗原复杂性和致癌物诱导肿瘤的异质性。在这里，我们采用了一种基因工程的、本土的小鼠肉瘤发生模型来研究癌症免疫编辑的过程。该系统使我们能够监测免疫原性和非免疫原性原位诱导肿瘤的发生和生长，这些肿瘤具有相同的遗传和组织病理学特征。通过比较具有免疫能力的小鼠与具有广泛免疫缺陷或特异性抗原耐受性的小鼠中肿瘤的发展，我们发现淋巴细胞对肿瘤特异性抗原（tsa）的识别对于针对肉瘤的免疫编辑至关重要。此外，通过选择性生长能够逃避T淋巴细胞攻击的细胞，对原发性肉瘤进行编辑，使其免疫原性降低。肿瘤抗原表达或MHCI呈递的缺失是发生这种免疫编辑过程的必要和充分条件。这些结果强调了TSA表达在免疫监视和潜在的免疫治疗中的重要性。
Cancer immunoediting is a process by which immune cells, particularly lymphocytes of the adaptive immune system, protect the host from the development of cancer and alter tumour progression by driving the outgrowth of tumour cells with decreased sensitivity to immune attack. Carcinogen-induced mouse models of cancer have shown that primary tumour susceptibility is enhanced in immune-compromised mice, while conversely, the capacity for such tumours to grow after transplantation into wild-type mice is reduced. However, many questions about the process of cancer immunoediting remain unanswered due, in part, to the known antigenic complexity and heterogeneity of carcinogen-induced tumours. Here we have adapted a genetically engineered, autochthonous mouse model of sarcomagenesis to investigate the process of cancer immunoediting. This system allowed us to monitor the onset and growth of immunogenic and non-immunogenic tumours induced in situ that harbor identical genetic and histopathological characteristics. By comparing the development of such tumours in immune-competent mice to mice with broad immunodeficiency or specific antigenic tolerance, we show that recognition of tumour-specific antigens (TSAs) by lymphocytes is critical for immunoediting against sarcomas. Furthermore, primary sarcomas were edited to become less immunogenic through the selective outgrowth of cells that were able to escape T lymphocyte attack. Loss of tumour antigen expression or MHCI presentation was necessary and sufficient for this immunoediting process to occur. These results highlight the importance of TSA expression in immune surveillance, and potentially, immunotherapy.
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影响因子：
64.8
作者：
Shankaran, V;Ikeda, H;Schreiber, RD
通讯作者：
Schreiber, RD
DOI：
10.1084/jem.185.4.695
发表时间：
1997-02-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dubey P;Hendrickson RC;Meredith SC;Siegel CT;Shabanowitz J;Skipper JC;Engelhard VH;Hunt DF;Schreiber H
通讯作者：
Schreiber H
DOI：
10.1084/jem.164.5.1516
发表时间：
1986-11-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Stauss HJ;Van Waes C;Fink MA;Starr B;Schreiber H
通讯作者：
Schreiber H
DOI：
10.1084/jem.157.3.1040
发表时间：
1983-03-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Uyttenhove C;Maryanski J;Boon T
通讯作者：
Boon T
影响因子：
32.4
作者：
Guerra, Nadia;Tan, Ying Xim;Raulet, David H.
通讯作者：
Raulet, David H.