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自噬、先天免疫反应与癌症。

Autophagy, the innate immune response and cancer.

机构信息

Cancer Research UK Beatson Institute, Garscube Estate, Glasgow, UK.

Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Glasgow, UK.

出版信息

Mol Oncol. 2020 Sep;14(9):1913-1929. doi: 10.1002/1878-0261.12774. Epub 2020 Aug 30.

Abstract

Autophagy is a cellular degradation and recycling system, which can interact with components of innate immune signalling pathways to enhance pathogen clearance, in both immune and nonimmune cells. Whilst this interaction is often beneficial for pathogen clearance, it can have varying outcomes in regard to tumorigenesis. Autophagy and the innate immune response can have both pro- and antitumorigenic effects at different stages of tumorigenesis due to the plastic nature of the tumour microenvironment (TME). Although both of these components have been studied in isolation as potential therapeutic targets, there has been less research concerning the interaction between autophagy and the innate immune response within the TME. As the innate immune response is critical for the formation of an effective antitumour adaptive immune response, targeting autophagy pathways in both tumour cells and innate immune cells could enhance tumour clearance. Within tumour cells, autophagy pathways are intertwined with pattern recognition receptor (PRR), inflammatory and cell death pathways, and therefore can alter the immunogenicity of the TME and development of the antitumour immune response. In innate immune cells, autophagy components can have autophagy-independent roles in functional pathways, and therefore could be valuable targets for enhancing immune cell function in the TME and immunotherapy. This review highlights the individual importance of autophagy and the innate immune response to tumorigenesis, and also explains the complex interactions between these pathways in the TME.

摘要

自噬是一种细胞降解和回收系统,可以与先天免疫信号通路的成分相互作用,增强免疫和非免疫细胞中的病原体清除。虽然这种相互作用通常有利于病原体清除,但它在肿瘤发生方面可能会产生不同的结果。自噬和先天免疫反应由于肿瘤微环境(TME)的可塑性,在肿瘤发生的不同阶段可以产生促肿瘤和抗肿瘤的作用。尽管这两个成分都作为潜在的治疗靶点进行了单独研究,但关于 TME 中自噬与先天免疫反应之间的相互作用的研究较少。由于先天免疫反应对于形成有效的抗肿瘤适应性免疫反应至关重要,因此靶向肿瘤细胞和先天免疫细胞中的自噬途径可以增强肿瘤清除。在肿瘤细胞中,自噬途径与模式识别受体(PRR)、炎症和细胞死亡途径交织在一起,因此可以改变 TME 的免疫原性和抗肿瘤免疫反应的发展。在先天免疫细胞中,自噬成分在功能途径中具有自噬非依赖性作用,因此可能是增强 TME 中免疫细胞功能和免疫治疗的有价值的靶点。这篇综述强调了自噬和先天免疫反应对肿瘤发生的个体重要性,并解释了这些途径在 TME 中的复杂相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f6e/7463325/0ea69fb44330/MOL2-14-1913-g001.jpg

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