Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
Department of Medical Microbiology, Immunology and Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, Springfield, IL, USA.
Adv Exp Med Biol. 2021;1316:191-211. doi: 10.1007/978-981-33-6785-2_12.
Immune checkpoints are essential for the regulation of immune cell functions. Although the abrogation of immunosurveillance of tumor cells is known, the regulators of immune checkpoints are not clear. Lipid metabolism is one of the important metabolic activities in organisms. In lipid metabolism, a large number of metabolites produced can regulate the gene expression and activation of immune checkpoints through various pathways. In addition, increasing evidence has shown that lipid metabolism leads to transient generation or accumulation of toxic lipids that result in endoplasmic reticulum (ER) stress and then regulate the transcriptional and posttranscriptional modifications of immune checkpoints, including transcription, protein folding, phosphorylation, palmitoylation, etc. More importantly, the lipid metabolism can also affect exosome transportation of checkpoints and the degradation of checkpoints by affecting ubiquitination and lysosomal trafficking. In this chapter, we mainly empathize on the roles of lipid metabolism in the regulation of immune checkpoints, such as gene expression, activation, and degradation.
免疫检查点对于免疫细胞功能的调节至关重要。虽然已知肿瘤细胞的免疫监视被废除，但免疫检查点的调节因子尚不清楚。脂质代谢是生物体的重要代谢活动之一。在脂质代谢中，大量产生的代谢产物可以通过多种途径调节免疫检查点的基因表达和激活。此外，越来越多的证据表明，脂质代谢导致毒性脂质的瞬时产生或积累，从而导致内质网（ER）应激，进而调节免疫检查点的转录和转录后修饰，包括转录、蛋白质折叠、磷酸化、棕榈酰化等。更重要的是，脂质代谢还可以通过影响泛素化和溶酶体运输来影响检查点的外泌体运输和检查点的降解。在本章中，我们主要强调了脂质代谢在调节免疫检查点方面的作用，如基因表达、激活和降解。
