Cellular senescence: Immunosurveillance and future immunotherapy
Cellular senescence: Immunosurveillance and future immunotherapy
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DOI：
10.1016/j.arr.2018.02.001
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发表时间：
2018-05-01
影响因子：
13.1
通讯作者：
Stolzing, Alexandra
中科院分区：
文献类型：
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作者：
Burton, Dominick G. A.;Stolzing, Alexandra
为了响应持续的DNA损伤，诱导细胞衰老促进免疫原性程序，其促进这些受损细胞的免疫清除。在生理条件下，衰老细胞可以激活先天性和适应性免疫反应，起到维持组织稳态的作用。此外，新的研究结果表明，细胞衰老的程序化诱导可能对调节生殖过程很重要，部分是由免疫清除促进的。然而，可能由于免疫系统的老化，未能消除衰老细胞可能会导致它们在组织中的持续存在，导致与年龄相关的疾病的发展和进展。这种免疫失败可能部分是由于免疫细胞中衰老程序的激活，导致其功能障碍。此外，在某些生物学背景下的衰老细胞已显示反而促进免疫抑制，这是一种可能反映急性与慢性衰老表型之间差异的反应。在这篇综述中，我们提供了一个关于衰老免疫存活的研究概述，包括对巨噬细胞识别衰老细胞的机制进行了重点讨论。还将讨论衰老免疫治疗策略作为去除衰老细胞的衰老药物的替代方案。
In response to persistent DNA damage, induction into cell senescence promotes an immunogenic program which facilitates immune clearance of these damaged cells. Under physiological conditions, senescent cells can activate both innate and adaptive immune responses, functioning to maintain tissue homeostasis. In addition, emerging findings suggest that programmed induction of cell senescence may be important for regulating reproductive processes, partly facilitated by immune clearance. However, likely owing to ageing of the immune system, a failure to eliminate senescent cells can contribute to their persistence in tissues, leading to the development and progression of age-related diseases. Such immune failure may in part be due to activation of the senescence program in immune cells, leading to their dysfunction. Furthermore, senescent cells under certain biological contexts have been shown to instead promote immune suppression, a response that may reflect differences between an acute verses chronic senescent phenotype. In this review, we provide an overview of the research to date concerning senescence immunosurviellance, including a focused discussion on the mechanisms by which macrophages may recognise senescent cells. Senescence immunotherapy strategies as an alternative to senolytics for the removal of senescent cells will also be discussed.