线粒体驱动的先天性免疫信号传导和炎症在癌症生长、免疫逃避和治疗抵抗中的作用。

3区 生物学 Q1 Biochemistry, Genetics and Molecular Biology
Sanjay Pandey, Vandana Anang, Michelle M Schumacher
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引用次数: 0

摘要

线粒体在细胞功能中发挥着多方面的重要作用,满足细胞的能量和生物合成需求。线粒体可调节细胞凋亡,同时对各种细胞外和细胞内应力做出反应,包括活性氧(ROS)、营养和氧气匮乏、内质网压力以及通过表面死亡受体发出的信号。线粒体的基本成分,如线粒体 DNA(mtDNA)、线粒体 RNA(mtRNA)、三磷酸腺苷(ATP)、心磷脂和甲酰肽是主要的损伤相关分子模式(DAMPs)。这些分子可激活细胞质(如 Retionoic Acid-Inducible Gene-1 (RIG-1) 和 Cyclic GMP-AMP Synthase (cGAS))和细胞表面(包括 Toll 样受体 (TLRs))的多种先天性免疫途径。这种激活级联导致释放各种细胞因子、趋化因子、干扰素、其他炎症分子和氧化物。先天性免疫通路进一步诱导肿瘤微环境中的慢性炎症,从而促进肿瘤细胞的生存和增殖,或促进上皮细胞向间质转化(EMT)、转移和抗药性。肿瘤中先天性炎症通路的长期激活也会促使免疫抑制检查点在癌细胞中表达,并促进免疫抑制群体(如髓系衍生抑制细胞(MDSCs)和调节性 T 细胞(Tregs))涌入癌细胞。因此,线粒体对细胞压力的感应可能会导致肿瘤生长增强。除此之外,肿瘤微环境也是免疫抑制细胞因子的来源。这些细胞因子会削弱免疫效应细胞的功能,从而促进免疫耐受和免疫逃避。在这里,我们描述了线粒体稳态和细胞应激的改变如何驱动肿瘤微环境中的先天性炎症通路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mitochondria driven innate immune signaling and inflammation in cancer growth, immune evasion, and therapeutic resistance.

Mitochondria play an important and multifaceted role in cellular function, catering to the cell's energy and biosynthetic requirements. They modulate apoptosis while responding to diverse extracellular and intracellular stresses including reactive oxygen species (ROS), nutrient and oxygen scarcity, endoplasmic reticulum stress, and signaling via surface death receptors. Integral components of mitochondria, such as mitochondrial DNA (mtDNA), mitochondrial RNA (mtRNA), Adenosine triphosphate (ATP), cardiolipin, and formyl peptides serve as major damage-associated molecular patterns (DAMPs). These molecules activate multiple innate immune pathways both in the cytosol [such as Retionoic Acid-Inducible Gene-1 (RIG-1) and Cyclic GMP-AMP Synthase (cGAS)] and on the cell surface [including Toll-like receptors (TLRs)]. This activation cascade leads to the release of various cytokines, chemokines, interferons, and other inflammatory molecules and oxidative species. The innate immune pathways further induce chronic inflammation in the tumor microenvironment which either promotes survival and proliferation or promotes epithelial to mesenchymal transition (EMT), metastasis and therapeutic resistance in the cancer cell's. Chronic activation of innate inflammatory pathways in tumors also drives immunosuppressive checkpoint expression in the cancer cells and boosts the influx of immune-suppressive populations like Myeloid-Derived Suppressor Cells (MDSCs) and Regulatory T cells (Tregs) in cancer. Thus, sensing of cellular stress by the mitochondria may lead to enhanced tumor growth. In addition to that, the tumor microenvironment also becomes a source of immunosuppressive cytokines. These cytokines exert a debilitating effect on the functioning of immune effector cells, and thus foster immune tolerance and facilitate immune evasion. Here we describe how alteration of the mitochondrial homeostasis and cellular stress drives innate inflammatory pathways in the tumor microenvironment.

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来源期刊
International review of cell and molecular biology
International review of cell and molecular biology BIOCHEMISTRY & MOLECULAR BIOLOGY-CELL BIOLOGY
CiteScore
7.70
自引率
0.00%
发文量
67
审稿时长
>12 weeks
期刊介绍: International Review of Cell and Molecular Biology presents current advances and comprehensive reviews in cell biology-both plant and animal. Articles address structure and control of gene expression, nucleocytoplasmic interactions, control of cell development and differentiation, and cell transformation and growth. Authored by some of the foremost scientists in the field, each volume provides up-to-date information and directions for future research.
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