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:Bidirectional regulation of lipid metabolism and the tumor microenvironment: new perspectives from mechanism to therapy.
Bidirectional regulation of lipid metabolism and the tumor microenvironment: new perspectives from mechanism to therapy.
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近年来,脂质代谢在癌症和免疫调节中的作用受到了广泛关注。脂质代谢重编程是癌症的关键标志之一,并通过支持肿瘤细胞的快速增殖、存活和转移,在癌症进展中发挥关键作用。重要的是,除了在癌细胞中已确立的功能外,脂质代谢还动态调节TME内多种免疫细胞(如T细胞、NK 细胞、巨噬细胞)的功能,从而塑造抗肿瘤免疫应答。本综述结合了当前对脂质代谢与TME之间相互作用的认识。我们首先简要概述癌细胞中的关键脂质代谢途径,随后深入探讨脂质摄取、合成和氧化影响肿瘤浸润免疫细胞命运和作用的方式。我们还评估了靶向脂质代谢的转化潜力,并提出将关键代谢酶抑制剂(例如脂肪酸合酶或乙酰辅酶A羧化酶)与免疫疗法联合,不仅能够有效缓解免疫抑制,还能克服免疫抑制。最后,我们着重指出尚存的知识空白,并提出未来的研究重点和潜力。干预脂质代谢相互作用为开发新型癌症治疗策略展现了广阔前景。
The role of lipid metabolism in cancer and immune regulation has received significant attention in recent years. Reprogramming of lipid metabolism is one of the key hallmarks of cancer and plays a critical role in cancer progression by supporting the rapid proliferation, survival, and metastasis of tumor cells.
Importantly, beyond its well-established functions in cancer cells, lipid metabolism dynamically regulates the functions of various immune cells within the TME (e. g. , T cells, natural killer cells, macrophages), thereby molding antitumor immune responses. This review combines the contemporary awareness of the reciprocal interactions between lipid metabolism and the TME.
We start with a simple overview of key lipid metabolic pathways in cancer cells, followed by an in-depth exploration of the way lipid uptake, synthesis, and oxidation influence the fate and role of tumor-infiltrating immune.
We also appraise the translational potential of targeting lipid metabolism and propose that combining inhibitors of key metabolic enzymes, for example fatty acid synthase or acetyl-CoA carboxylase, with immunotherapy can not only effectively alleviate immunosuppression but also overcome immunosuppression.
Finally, we spotlight the remaining knowledge gaps and put forward future research priorities and potential. Intervening in lipid metabolic interactions represents a promising prospect for developing the novel cancer treatment strategies.
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