Department of Pediatrics, Division of Blood and Marrow Transplantation and Cellular Therapies, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Curr Opin Hematol. 2020 Nov;27(6):353-359. doi: 10.1097/MOH.0000000000000615.
Controlling T cell activity through metabolic manipulation has become a prominent feature in immunology and practitioners of both adoptive cellular therapy (ACT) and haematopoietic stem cell transplantation (HSCT) have utilized metabolic interventions to control T cell function. This review will survey recent metabolic research efforts in HSCT and ACT to paint a broad picture of immunometabolism and highlight advances in each area.
In HSCT, recent publications have focused on modifying reactive oxygen species, sirtuin signalling or the NAD salvage pathway within alloreactive T cells and regulatory T cells. In ACT, metabolic interventions that bolster memory T cell development, increase mitochondrial density and function, or block regulatory signals in the tumour microenvironment (TME) have recently been published.
Metabolic interventions control immune responses. In ACT, efforts seek to improve the in-vivo metabolic fitness of T cells, while in HSCT energies have focused on blocking alloreactive T cell expansion or promoting regulatory T cells. Methods to identify new, metabolically targetable pathways, as well as the ability of metabolic biomarkers to predict disease onset and therapeutic response, will continue to advance the field towards clinically applicable interventions.
通过代谢调控来控制 T 细胞活性已成为免疫学的一个显著特征,细胞过继免疫治疗(ACT)和造血干细胞移植(HSCT)的从业者都利用代谢干预来控制 T 细胞功能。这篇综述将调查 HSCT 和 ACT 中的代谢研究进展,以全面了解免疫代谢,并强调每个领域的进展。
在 HSCT 中,最近的出版物集中在修饰同种反应性 T 细胞和调节性 T 细胞中的活性氧、沉默调节蛋白信号或烟酰胺腺嘌呤二核苷酸(NAD)补救途径。在 ACT 中,最近发表了一些代谢干预措施,这些措施可以促进记忆 T 细胞的发育、增加线粒体密度和功能,或阻断肿瘤微环境(TME)中的调节信号。
代谢干预控制免疫反应。在 ACT 中,人们努力提高 T 细胞的体内代谢适应性,而在 HSCT 中,人们则专注于阻止同种反应性 T 细胞的扩增或促进调节性 T 细胞的增殖。识别新的、可代谢靶向的途径的方法,以及代谢生物标志物预测疾病发作和治疗反应的能力,将继续推动该领域朝着临床应用的干预措施发展。