RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Lactate: a rising star in tumors and inflammation.
Lactate: a rising star in tumors and inflammation.
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乳酸传统上被视为糖酵解的单纯副产物或代谢废物。然而,越来越多的文献表明其在调节多种生理和病理过程中发挥关键作用。乳酸通常与缺氧、炎症、病毒感染和肿瘤相关。它通过激活单羧酸转运蛋白(MCT)或G蛋白偶联受体GPR81跨细胞膜发挥复杂的生理作用。乳酸通过调节多种免疫细胞(如NK 细胞、T细胞、树突状细胞和单核细胞)的功能发挥免疫抑制作用,并在肿瘤微环境中参与巨噬细胞极化和髓源性抑制细胞(MDSC)分化。近期还发现乳酸可增加CD8+ T细胞密度,从而增强抗肿瘤免疫应答。急性或慢性炎症性疾病在炎症疾病微环境中具有相反的免疫状态。细胞类型、转录调节因子、离子介质和微环境等因素共同促成了乳酸所表现出的多样化功能。本文综述了乳酸在肿瘤微环境和炎症条件下对免疫细胞多种功能调节的多效性作用,这可能有助于为炎症性疾病和恶性肿瘤的诊断与治疗提供新的见解和潜在靶点。
Lactate has been traditionally regarded as a mere byproduct of glycolysis or metabolic waste.
However, an increasing body of literature suggests its critical role in regulating various physiological and pathological processes. Lactate is generally associated with hypoxia, inflammation, viral infections, and tumors. It performs complex physiological roles by activating monocarboxylate transporter (MCT) or the G protein-coupled receptor GPR81 across the cell membrane. Lactate exerts immunosuppressive effects by regulating the functions of various immune cells (such as natural killer cells, T cells, dendritic cells, and monocytes) and its role in macrophage polarization and myeloid-derived suppressor cell (MDSC) differentiation in the tumor microenvironment.
Lactic acid has also recently been found to increase the density of CD8 + T cells, thereby enhancing the antitumor immune response. Acute or chronic inflammatory diseases have opposite immune states in the inflammatory disease microenvironment. Factors such as cell types, transcriptional regulators, ionic mediators, and the microenvironment all contribute to the diverse functions lactate exhibits.
Herein, we reviewed the pleiotropic effects of lactate on the regulation of various functions of immune cells in the tumor microenvironment and under inflammatory conditions, which may help to provide new insights and potential targets for the diagnosis and treatment of inflammatory diseases and malignancies.
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