脂质代谢在癌症进展中对 CD8+ T 细胞的调控。
Regulation of CD8+ T cells by lipid metabolism in cancer progression.
机构信息
Department of Molecular Biology, Princeton University, Princeton, NJ, 08544, USA.
Ludwig Institute for Cancer Research Princeton Branch, Princeton, NJ, 08544, USA.
出版信息
Cell Mol Immunol. 2024 Nov;21(11):1215-1230. doi: 10.1038/s41423-024-01224-z. Epub 2024 Oct 14.
Dysregulation of lipid metabolism is a key characteristic of the tumor microenvironment, where tumor cells utilize lipids for proliferation, survival, metastasis, and evasion of immune surveillance. Lipid metabolism has become a critical regulator of CD8+ T-cell-mediated antitumor immunity, with excess lipids in the tumor microenvironment impeding CD8+ T-cell activities. Considering the limited efficacy of immunotherapy in many solid tumors, targeting lipid metabolism to enhance CD8+ T-cell effector functions could significantly improve immunotherapy outcomes. In this review, we examine recent findings on how lipid metabolic processes, including lipid uptake, synthesis, and oxidation, regulate CD8+ T cells within tumors. We also assessed the impact of different lipids on CD8+ T-cell-mediated antitumor immunity, with a particular focus on how lipid metabolism affects mitochondrial function in tumor-infiltrating CD8+ T cells. Furthermore, as cancer is a systemic disease, we examined systemic factors linking lipid metabolism to CD8+ T-cell effector function. Finally, we summarize current therapeutic approaches that target lipid metabolism to increase antitumor immunity and enhance immunotherapy. Understanding the molecular and functional interplay between lipid metabolism and CD8+ T cells offers promising therapeutic opportunities for cancer treatment.
脂质代谢失调是肿瘤微环境的一个关键特征,肿瘤细胞利用脂质进行增殖、存活、转移和逃避免疫监视。脂质代谢已成为 CD8+T 细胞介导的抗肿瘤免疫的关键调节因子,肿瘤微环境中过多的脂质会阻碍 CD8+T 细胞的活性。鉴于免疫疗法在许多实体瘤中的疗效有限,靶向脂质代谢以增强 CD8+T 细胞效应功能可能会显著改善免疫治疗的效果。在这篇综述中,我们研究了最近关于脂质代谢过程(包括脂质摄取、合成和氧化)如何在肿瘤内调节 CD8+T 细胞的发现。我们还评估了不同脂质对 CD8+T 细胞介导的抗肿瘤免疫的影响,特别关注脂质代谢如何影响肿瘤浸润的 CD8+T 细胞中的线粒体功能。此外,由于癌症是一种全身性疾病,我们研究了将脂质代谢与 CD8+T 细胞效应功能联系起来的系统因素。最后,我们总结了目前靶向脂质代谢以增加抗肿瘤免疫和增强免疫治疗的治疗方法。了解脂质代谢和 CD8+T 细胞之间的分子和功能相互作用为癌症治疗提供了有前途的治疗机会。