Helmholtz Centre for Infection Research, Braunschweig, Germany.
Carcinogenesis. 2012 Jun;33(6):1123-6. doi: 10.1093/carcin/bgs124. Epub 2012 Apr 2.
Cellular senescence, a state of stable growth arrest, can occur in response to various stress stimuli such as telomere shortening, treatment with chemotherapeutic drugs or the aberrant activation of oncogenes. Senescent cells communicate with their environment by secreting various cytokines and growth factors, and it has become clear that this 'secretory phenotype' can have pro- as well as anti-tumorigenic effects. Recent work from our laboratory showed that premalignant, senescent hepatocytes are recognized and cleared through an antigen-specific immune response and that this immune response, designated as 'senescence surveillance' is crucial for tumor suppression in the liver [(Kang,T.W. et al. (2011) Senescence surveillance of pre-malignant hepatocytes limits liver cancer development. Nature, 479, 547-551]. It is an emerging concept that immune responses against senescent cells have a broader biological significance in cancer- as well as non-cancer pathologies and current data suggest that distinct immune responses are engaged to clear senescent cells in different disease settings. In this review article, we will discuss different examples how immune responses against senescent cells are involved to restrict disease progression in cancer- and non-cancer pathologies.
细胞衰老,一种稳定生长停滞的状态,可以响应各种应激刺激而发生,如端粒缩短、化疗药物治疗或癌基因的异常激活。衰老细胞通过分泌各种细胞因子和生长因子与环境进行通讯,现在已经很清楚,这种“分泌表型”既可以促进肿瘤发生,也可以抑制肿瘤发生。我们实验室最近的工作表明,恶性前体、衰老的肝细胞通过抗原特异性免疫反应被识别和清除,这种免疫反应被称为“衰老监测”,对于肝脏中的肿瘤抑制至关重要[(Kang, T.W.等人(2011)恶性前体肝细胞的衰老监测限制肝癌的发展。自然,479, 547-551]。一个新兴的概念是,针对衰老细胞的免疫反应在癌症和非癌症病理中具有更广泛的生物学意义,目前的数据表明,在不同的疾病环境中,清除衰老细胞需要不同的免疫反应。在这篇综述文章中,我们将讨论不同的例子,说明针对衰老细胞的免疫反应如何参与限制癌症和非癌症病理中的疾病进展。
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