11月24日，nature雜志在線發(fā)表了德國研究人員的最新研究成果,，揭示了肝細(xì)胞癌變前的衰老監(jiān)測(cè)可以限制肝癌的發(fā)展,。致癌基因誘導(dǎo)的衰老曾被發(fā)現(xiàn)起一個(gè)內(nèi)在腫瘤抑制機(jī)制的作用,。Lars Zender及其同事提出了“衰老監(jiān)測(cè)”的概念：他們發(fā)現(xiàn)，惡變前的衰老肝細(xì)胞能通過一個(gè)由腫瘤抗原引導(dǎo)的免疫反應(yīng)被清除,。這個(gè)過程需要CD4+ T細(xì)胞的參與,，并且在小鼠模型中抑制肝癌的發(fā)展。本文作者們還提供了這樣的證據(jù)：衰老肝細(xì)胞會(huì)在免疫系統(tǒng)被抑制的患者肝臟中積累,，說明衰老監(jiān)測(cè)對(duì)人類也可能行得通,。設(shè)計(jì)用來利用對(duì)惡變前的衰老細(xì)胞進(jìn)行抗原特異性免疫監(jiān)測(cè)的策略在癌癥預(yù)防和治療中可能會(huì)有潛力，而這種類型的抗原特異性免疫反應(yīng)在疫苗生產(chǎn)中也可能會(huì)有用,。（生物谷Bioon.com）
doi:10.1038/nature10599
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Senescence surveillance of pre-malignant hepatocytes limits liver cancer development
Tae-Won Kang, Tetyana Yevsa, Norman Woller, Lisa Hoenicke, Torsten Wuestefeld, Daniel Dauch, Anja Hohmeyer, Marcus Gereke, Ramona Rudalska, Anna Potapova, Marcus Iken, Mihael Vucur, Siegfried Weiss, Mathias Heikenwalder, Sadaf Khan, Jesus Gil, Dunja Bruder, Michael Manns, Peter Schirmacher, Frank Tacke, Michael Ott, Tom Luedde, Thomas Longerich, Stefan Kubicka & Lars Zender
Upon the aberrant activation of oncogenes, normal cells can enter the cellular senescence program, a state of stable cell-cycle arrest, which represents an important barrier against tumour development in vivo. Senescent cells communicate with their environment by secreting various cytokines and growth factors, and it was reported that this ‘secretory phenotype’ can have pro- as well as anti-tumorigenic effects. Here we show that oncogene-induced senescence occurs in otherwise normal murine hepatocytes in vivo. Pre-malignant senescent hepatocytes secrete chemo- and cytokines and are subject to immune-mediated clearance (designated as ‘senescence surveillance’), which depends on an intact CD4+ T-cell-mediated adaptive immune response. Impaired immune surveillance of pre-malignant senescent hepatocytes results in the development of murine hepatocellular carcinomas (HCCs), thus showing that senescence surveillance is important for tumour suppression in vivo. In accordance with these observations, ras-specific Th1 lymphocytes could be detected in mice, in which oncogene-induced senescence had been triggered by hepatic expression of NrasG12V. We also found that CD4+ T cells require monocytes/macrophages to execute the clearance of senescent hepatocytes. Our study indicates that senescence surveillance represents an important extrinsic component of the senescence anti-tumour barrier, and illustrates how the cellular senescence program is involved in tumour immune surveillance by mounting specific immune responses against antigens expressed in pre-malignant senescent cells.
