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Senescence in the Development and Response to Cancer with Immunotherapy: A Double-Edged Sword

免疫治疗在癌症发生和反应中的衰老: 一把双刃剑

  • 影响因子:4.32
  • DOI:10.3390/ijms21124346
  • 作者列表:"Anthony M. Battram","Mireia Bachiller","Beatriz Martín-Antonio
  • 发表时间:2020-06-19
Abstract

Cellular senescence was first described as a physiological tumor cell suppressor mechanism that leads to cell growth arrest with production of the senescence-associated secretory phenotype known as SASP. The main role of SASP in physiological conditions is to attract immune cells to clear senescent cells avoiding tumor development. However, senescence can be damage-associated and, depending on the nature of these stimuli, additional types of senescence have been described. In the context of cancer, damage-associated senescence has been described as a consequence of chemotherapy treatments that were initially thought of as a tumor suppressor mechanism. However, in certain contexts, senescence after chemotherapy can promote cancer progression, especially when immune cells become senescent and cannot clear senescent tumor cells. Moreover, aging itself leads to continuous inflammaging and immunosenescence which are responsible for rewiring immune cells to become defective in their functionality. Here, we define different types of senescence, pathways that activate them, and functions of SASP in these events. Additionally, we describe the role of senescence in cancer and its treatments, including how aging and chemotherapy contribute to senescence in tumor cells, before focusing on immune cell senescence and its role in cancer. Finally, we discuss potential therapeutic interventions to reverse cell senescence.

摘要

细胞衰老最初被描述为一种生理性肿瘤细胞抑制机制,导致细胞生长停滞,产生衰老相关的分泌表型,称为 SASP。SASP 在生理条件下的主要作用是吸引免疫细胞清除衰老细胞,避免肿瘤发展。然而,衰老可能与损伤相关,并且根据这些刺激的性质,已经描述了其他类型的衰老。在癌症的背景下,损伤相关的衰老被描述为最初被认为是肿瘤抑制机制的化疗治疗的结果。然而,在某些情况下,化疗后的衰老可以促进癌症进展,特别是当免疫细胞变得衰老并且不能清除衰老的肿瘤细胞时。此外,衰老本身会导致持续的炎症和免疫衰老,这些炎症和免疫衰老负责重新连接免疫细胞,使其功能变得有缺陷。在这里,我们定义了不同类型的衰老,激活它们的途径,以及 SASP 在这些事件中的功能。此外,在关注免疫细胞衰老及其在癌症中的作用之前,我们描述了衰老在癌症及其治疗中的作用,包括衰老和化疗如何促进肿瘤细胞衰老。最后,我们讨论了逆转细胞衰老的潜在治疗干预措施。

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