He Yijiang, Qiu Yue, Yang Xiansong, Lu Guimei, Zhao Shan-Shan
Abdominal Radiation Oncology Ward II, Cancer Hospital of China Medical University, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning 110042, China.
Department of Digestive Diseases 1, Cancer Hospital of China Medical University, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning 110042, China.
Semin Cancer Biol. 2025 Jan;108:17-32. doi: 10.1016/j.semcancer.2024.11.002. Epub 2024 Nov 23.
Cellular senescence is a response to various stress signals, which is characterized by stable cell cycle arrest, alterations in cellular morphology, metabolic reprogramming and production of senescence-associated secretory phenotype (SASP). When it occurs in the immune system, it is called immunosenescence. Cervical cancer is a common gynecological malignancy, and cervical cancer screening is generally recommended before the age of 65. Elderly women (≥65 years) are more often diagnosed with advanced disease and have poorer prognosis compared to younger patients. Despite extensive research, the tumor microenvironment requires more in-depth exploration, particularly in elderly patients. In cervical cancer, senescent cells have a double-edged sword effect on tumor progression. Induction of preneoplastic cell senescence prevents tumor initiation, and several treatment approaches of cervical cancer act in part by inducing cancer cell senescence. However, senescent immune cell populations within the tumor microenvironment facilitate tumor development, recurrence, treatment resistance, etc. Amplification of beneficial effects and inhibition of aging-related pro-tumorigenic pathways contribute to improving antitumor effects. This review discusses senescent cancer and immune cells present in the tumor microenvironment of cervical cancer and how these senescent cells and their SASP remodel the tumor microenvironment, influence antitumor immunity and tumor initiation and development. Moreover, we discuss the significance of senotherapeutics that enable to eliminate senescent cells and prevent tumor progression and development through improving antitumor immunity and affecting the tumor microenvironment.
细胞衰老 是对各种应激信号的一种反应，其特征为稳定的细胞周期停滞、细胞形态改变、代谢重编程以及衰老相关分泌表型（SASP）的产生。当它发生在免疫系统中时，被称为免疫衰老。宫颈癌是一种常见的妇科恶性肿瘤，一般建议在65岁之前进行宫颈癌筛查。老年女性（≥65岁）相较于年轻患者更常被诊断为晚期疾病，且预后较差。尽管进行了广泛研究，但肿瘤微环境仍需要更深入的探索，尤其是在老年患者中。在宫颈癌中，衰老细胞对肿瘤进展具有双刃剑效应。诱导癌前细胞衰老可预防肿瘤发生，并且几种宫颈癌治疗方法部分是通过诱导癌细胞衰老起作用的。然而，肿瘤微环境中的衰老免疫细胞群体促进肿瘤发展、复发、治疗抵抗等。放大有益作用并抑制与衰老相关的促肿瘤发生途径有助于提高抗肿瘤效果。本综述讨论了宫颈癌肿瘤微环境中存在的衰老癌细胞和免疫细胞，以及这些衰老细胞及其SASP如何重塑肿瘤微环境、影响抗肿瘤免疫以及肿瘤的起始和发展。此外，我们还讨论了衰老疗法的意义，即通过改善抗肿瘤免疫和影响肿瘤微环境来消除衰老细胞并预防肿瘤进展和发展。
