CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Pyroptosis: Turning Up the Heat on Cancer.
Pyroptosis: Turning Up the Heat on Cancer.
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抗肿瘤免疫的主要效应细胞是识别并消灭肿瘤细胞的杀伤性淋巴细胞。肿瘤细胞与正常细胞极为相似,这对抗肿瘤免疫控制构成了挑战。需要来自肿瘤或来自摄取濒死肿瘤细胞的抗原呈递细胞的危险信号,才能将肿瘤细胞与正常细胞区分开来,从而充分激活杀伤细胞的效应功能和记忆,进而控制肿瘤。肿瘤细胞如何死亡,强烈影响免疫系统是否将其视为危险。肿瘤中固有免疫的激活,包括干扰素信号传导和坏死性细胞死亡(如坏死性凋亡和焦亡),会发出强烈的免疫警报。焦亡通过产生炎症性肿瘤微环境在肿瘤免疫中发挥重要作用。然而,它是一把双刃剑,既能促进肿瘤发生,也能提高癌症治疗的有效性和细胞毒性。在本文中,我们综述了关于肿瘤细胞焦亡——可以说是最具炎症性的细胞死亡类型——在抗肿瘤免疫中作用的已知信息,并讨论能否安全地利用它来拓宽对免疫治疗有响应的肿瘤范围。
The major effector cells of antitumor immunity are killer lymphocytes that recognize and eliminate tumor cells. The fact that tumor cells look a lot like normal cells poses a challenge to antitumor immune control. A danger signal from the tumor or from antigen-presenting cells that have taken up dying tumor cells is needed to distinguish tumor cells from normal cells to fully activate killer cell effector functionality and memory and thereby control the tumor.
How a tumor cell dies strongly affects whether the immune system sees it as dangerous. Activation of innate immunity in the tumor, including interferon signaling and necrotic cell death (e. g. , necroptosis and pyroptosis), sounds a potent immune alarm. Pyroptosis plays an important role in tumor immunity by generating an inflamed tumor microenvironment.
However, it is a double-edged sword that can both promote tumorigenesis and increase the effectiveness and cytotoxicity of cancer therapy. In this article, we review what is known about the role of tumor cell pyroptosis, which is arguably the most inflammatory type of cell death, in antitumor immunity and discuss whether it could be safely harnessed to broaden the range of tumors that respond to immunotherapy.
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