Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, China.
Front Immunol. 2024 Jan 12;14:1309635. doi: 10.3389/fimmu.2023.1309635. eCollection 2023.
Programmed cell death (PCD) is an evolutionarily conserved mechanism of cell suicide that is controlled by various signaling pathways. PCD plays an important role in a multitude of biological processes, such as cell turnover, development, tissue homeostasis and immunity. Some forms of PCD, including apoptosis, autophagy-dependent cell death, pyroptosis, ferroptosis and necroptosis, contribute to carcinogenesis and cancer development, and thus have attracted increasing attention in the field of oncology. Recently, increasing research-based evidence has demonstrated that PCD acts as a critical modulator of tumor immunity. PCD can affect the function of innate and adaptive immune cells, which leads to distinct immunological consequences, such as the priming of tumor-specific T cells, immunosuppression and immune evasion. Targeting PCD alone or in combination with conventional immunotherapy may provide new options to enhance the clinical efficacy of anticancer therapeutics. In this review, we introduce the characteristics and mechanisms of ubiquitous PCD pathways (e.g., apoptosis, autophagy-dependent cell death, pyroptosis and ferroptosis) and explore the complex interaction between these cell death mechanisms and tumor immunity based on currently available evidence. We also discuss the therapeutic potential of PCD-based approaches by outlining clinical trials targeting PCD in cancer treatment. Elucidating the immune-related effects of PCD on cancer pathogenesis will likely contribute to an improved understanding of oncoimmunology and allow PCD to be exploited for cancer treatment.
程序性细胞死亡(PCD)是一种受多种信号通路控制的细胞自杀的进化保守机制。PCD 在许多生物学过程中发挥着重要作用,如细胞更替、发育、组织稳态和免疫。一些形式的 PCD,包括细胞凋亡、自噬依赖性细胞死亡、细胞焦亡、铁死亡和坏死性凋亡,有助于癌症的发生和发展,因此在肿瘤学领域引起了越来越多的关注。最近,越来越多的基于研究的证据表明,PCD 是肿瘤免疫的关键调节剂。PCD 可以影响先天和适应性免疫细胞的功能,从而导致不同的免疫后果,如肿瘤特异性 T 细胞的启动、免疫抑制和免疫逃逸。靶向 PCD 单独或与常规免疫疗法联合使用可能为增强抗癌治疗的临床疗效提供新的选择。在这篇综述中,我们介绍了普遍存在的 PCD 途径(如细胞凋亡、自噬依赖性细胞死亡、细胞焦亡和铁死亡)的特征和机制,并根据现有证据探讨了这些细胞死亡机制与肿瘤免疫之间的复杂相互作用。我们还通过概述针对癌症治疗中 PCD 的临床试验,讨论了基于 PCD 的方法的治疗潜力。阐明 PCD 对癌症发病机制的免疫相关影响可能有助于更好地理解肿瘤免疫学,并为癌症治疗利用 PCD 提供依据。
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