线粒体在细胞功能中发挥着重要的多方面作用，满足细胞的能量和生物合成需求。它们调节细胞凋亡，同时响应不同的细胞外和细胞内应激，包括活性氧 (ROS)、营养和氧缺乏、内质网应激以及通过表面死亡受体的信号传导。线粒体的组成部分，如线粒体 DNA (mtDNA)、线粒体 RNA (mtRNA)、三磷酸腺苷 (ATP)、心磷脂和甲酰基肽，是主要的损伤相关分子模式 (DAMP)。这些分子激活细胞质中的多种先天免疫途径[例如维甲酸诱导基因1 (RIG-1) 和环 GMP-AMP 合酶 (cGAS)] 和细胞表面上的[包括 Toll 样受体 (TLR)] ]。这种激活级联导致各种细胞因子、趋化因子、干扰素和其他炎症分子和氧化物质的释放。先天免疫途径进一步诱导肿瘤微环境中的慢性炎症，从而促进癌细胞的存活和增殖或促进上皮间质转化（EMT）、转移和治疗耐药。肿瘤中先天炎症通路的慢性激活还会驱动癌细胞中免疫抑制检查点的表达，并促进癌症中骨髓源性抑制细胞 (MDSC) 和调节性 T 细胞 (Treg) 等免疫抑制细胞群的流入。因此，线粒体对细胞应激的感知可能会导致肿瘤生长增强。除此之外，肿瘤微环境也成为免疫抑制细胞因子的来源。这些细胞因子对免疫效应细胞的功能产生削弱作用，从而促进免疫耐受并促进免疫逃避。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炎症途径。版权所有 © 2024。由爱思唯尔公司出版。

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.Copyright © 2024. Published by Elsevier Inc.