CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Immunogenicity of cancer cells: An overview.
Immunogenicity of cancer cells: An overview.
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免疫系统在机体识别并消灭恶性细胞的能力中发挥关键作用。癌细胞的免疫原性是指其诱发免疫应答的能力。免疫原性是制定成功免疫治疗策略的关键决定因素。免疫治疗策略包括免疫检查点抑制剂、嵌合抗原受体(CAR)T细胞疗法和疫苗。免疫原性细胞死亡(ICD)是一种能够引发针对濒死细胞免疫应答的细胞死亡形式。ICD的特征是释放特定分子以激活免疫系统,进而由免疫细胞识别并清除濒死细胞。ICD现象的一个显著特征是:启动程序性死亡、但尚未完全凋亡的细胞会大量释放三磷酸腺苷(ATP)。ICD由细胞死亡期间一系列分子事件启动,包括濒死细胞暴露或释放钙网蛋白、高迁移率族蛋白B1(HMGB1)和ATP等分子。这些分子充当“吃我”信号,可被免疫细胞识别,促使包括吞噬细胞在内的免疫细胞通过程序性坏死、凋亡和焦亡等多种途径吞噬并降解濒死细胞。本文综述我们目前对针对濒死细胞的免疫应答之病理生理学意义及其激活机制的认识。
总体而言,ICD是免疫系统识别并清除濒死细胞(包括癌细胞)的重要机制。了解ICD的分子事件,有望催生利用免疫系统力量对抗癌症的新型疗法。
The immune system assumes a pivotal role in the organism's capacity to discern and obliterate malignant cells. The immunogenicity of a cancer cell pertains to its proficiency in inciting an immunological response. The prowess of immunogenicity stands as a pivotal determinant in the triumph of formulating immunotherapeutic methodologies. Immunotherapeutic strategies include immune checkpoint inhibitors, chimeric antigen receptor (CAR) T-cell therapy, and on vaccines. Immunogenic cell death (ICD) epitomizes a form of cellular demise that incites an immune response against dying cells. ICD is characterized by the liberation of distinct specific molecules that activate the immune system, thereby leading to the identification and elimination of dying cells by immunocytes.
One of the salient characteristics inherent to the ICD phenomenon resides in the vigorous liberation of adenosine triphosphate (ATP) by cellular entities dedicated to embarking upon the process of programmed cell death, yet refraining from complete apoptotic demise. ICD is initiated by a sequence of molecular events that occur during cell death.
These occurrences encompass the unveiling or discharge of molecules such as calreticulin, high-mobility group box 1 (HMGB1), and adenosine triphosphate (ATP) from dying cells. These molecules act as "eat me" signals, which are recognized by immune cells, thereby prompting the engulfment and deterioration of expiring cells by phagocytes including various pathways such as Necroptosis, Apoptosis, and pyroptosis.
Here, we review our current understanding of the pathophysiological importance of the immune responses against dying cells and the mechanisms underlying their activation.
Overall, the ICD represents an important mechanism by which the immune system recognizes and eliminates dying cells, including cancer cells. Understanding the molecular events that underlie ICD bears the potential to engender innovative cancer therapeutics that harness the power of the immune system to combat cancer.
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